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Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration
Abstract
We determined the distribution and biocompatibility of graphene oxide (GO) in mice by using radiotracer technique and a series of biological assays. Results showed that GO was predominantly deposited in the lungs, where it was retained for a long time. Compared with other carbon nanomaterials, GO exhibited long blood circulation time (half-time 5.3 ± 1.2 h), and low uptake in reticuloendothelial system. No pathological changes were observed in examined organs when mice were exposed to 1 mg kg−1 body weight of GO for 14 days. Moreover, GO showed good biocompatibility with red blood cells. These results suggested that GO might be a promising material for biomedical applications, especially for targeted drug delivery to the lung. However, due to its high accumulation and long time retention, significant pathological changes, including inflammation cell infiltration, pulmonary edema and granuloma formation were found at the dosage of 10 mg kg−1 body weight. More attention should be paid to the toxicity of GO.Graphical abstractResearch highlights► GO can be effectively labeled with 188Re. ► 188Re–GO was predominantly deposited in the lungs. ► GO shows good biocompatibility to targeted organs. ► GO shows good biocompatibility to RBC. ► Provided basic information for toxicity assessment and biomedical applications.
... These mechanisms of toxicity of GNPs Along with sharpened edges of GDs can end in cell membrane destruction. In these mechanisms, toll-like receptors-(TLR-), transforming growth factor β-(TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent pathways are involved, and oxidative stress plays an important role therein (Ou et al. 2016, Zhang et al. 2011. ...
... In animals, inhalation, oral administration, intravenous injection, intraperitoneal injection and subcutaneous injection are the commonly known pathways to exposure (Zhang et al. 2011). But GO-PEG and FLG do not show evident gastrointestinal tract absorption or tissue uptake via oral administration (Yang et al. 2013). ...
... But GO-PEG and FLG do not show evident gastrointestinal tract absorption or tissue uptake via oral administration (Yang et al. 2013). Zhang et al. (2011) reported that GDs can deposit and accumulate in the mice lungs, to a high level, for more than 3 months (Zhang et al. 2011). Some studies show that graphene circulates through the body of mice in 30 minutes, and can accumulate in the liver and bladder tissues (Wen et al. 2015, Singh et al. 2011. ...
... Importantly, the majority of safety investigations involves an injection of GBMs, e.g. intravenous (iv), often resulting in organ-specific biodistribution, accumulation and subsequent inflammation [31]. These investigations, however, are often not relevant for applications in regenerative medicine. ...
... mg/kg) was substantially lower compared to various previous reports (10-14.4 mg/kg) that showed organ-specific toxicity [31,68]. Nevertheless, in view of local implantation, the amount used here can still be regarded as substantial. ...
Despite the immense need for effective treatment of spinal cord injury (SCI), no successful repair strategy has yet been clinically implemented. Multifunctional biomaterials, based on porcine adipose tissue-derived extracellular matrix (adECM) and reduced graphene oxide (rGO), were recently shown to stimulate in vitro neural stem cell growth and differentiation. Nevertheless, their functional performance in clinically more relevant in vivo conditions remains largely unknown. Before clinical application of these adECM-rGO nanocomposites can be considered, a rigorous assessment of the cytotoxicity and biocompatibility of these biomaterials is required. For instance, xenogeneic adECM scaffolds could still harbour potential immunogenicity following decellularization. In addition, the toxicity of rGO has been studied before, yet often in experimental settings that do not bear relevance to regenerative medicine. Therefore, the present study aimed to assess both the in vitro as well as in vivo safety of adECM and adECM-rGO scaffolds. First, pulmonary, renal and hepato-cytotoxicity as well as macrophage polarization studies showed that scaffolds were benign invitro. Then, a laminectomy was performed at the 10th thoracic vertebra, and scaffolds were implanted directly contacting the spinal cord. For a total duration of 6 weeks, animal welfare was not negatively affected. Histological analysis demonstrated the degradation of adECM scaffolds and subsequent tissue remodeling. Graphene-based scaffolds showed a very limited fibrous encapsulation, while rGO sheets were engulfed by foreign body giant cells. Furthermore, all scaffolds were infiltrated by macrophages, which were largely polarized towards a pro-regenerative phenotype. Lastly, organ-specific histopathology and biochemical analysis of blood did not reveal any adverse effects. In summary, both adECM and adECM-rGO implants were biocompatible upon laminectomy while establishing a pro-regenerative microenvironment, which justifies further research on their therapeutic potential for treatment of SCI.
... Напомним еще раз, что вопросы «ингаляционной токсичности» стоят остро в отношении к любым наноматериалам, а не только наноструктурам углерода [17,24], так как она определяется, в первую очередь, размерами частиц и лишь затем химическими и биологическими свойствами материала. Об этом, в частности, свидетельствуют и данные работы [31], в которой показано, что токсическое действие МСУНТ (диаметр ~20 нм, отношение размеров [80][81][82][83][84][85][86][87][88][89][90], углеродных нанонитей (диаметр ~150 нм, отношение размеров 30-40) и наночастиц углерода (carbon black, отношение размеров 1) in vitro на культуре клеток зависит от размера наночастиц. ...
... Так, установлено, что печень является основным органом, ответственным за накопление маленьких частиц GO, тогда как большие частицы накапливаются в легких [82,83]. Зависит от размера и экскреция GOчастицы небольших размеров выводятся через почки [84]. При этом покрытие ПЭГ частиц GO ослабляет вызываемые ими повреждения тканей (печени, легких и почек, а также хронический фиброз печени и легких) [85]. ...
BACKGROUND: Gestosis (preeclampsia) is an important problem of modern obstetrics. Despite the improvement of methods of prevention and treatment, there is an increase in the rate of this pregnancy complication. In this regard, the search for new approaches to the treatment of preeclampsia is an important problem of modern perinatology. AIM: The aim of this study is studying of the effect of taurine on experimental gestosis in rats. MATERIALS AND METHODS: Preeclampsia was induced on female rats by sodium nitrite and lipopolysaccharide. 2-aminoethanesulfonic acid was administered at a dose of 44.3 mg / kg (in terms of taurine) from the 16th to the 19th day of pregnancy. The number of implantation sites, resorption sites, live fetuses, weight of placentas and fetuses, lactate dehydrogenase activity, content of lactic and pyruvic acids, nitric oxide, malondialdehyde and creatine were evaluated. RESULTS: It has been shown that 2-aminoethanesulfonic acid leads to normalization of the metabolic processes (the level of malondialdehyde, nitric oxide, lactate and lactate dehydrogenase activity) in the body of pregnant female rats with induced preeclampsia in the last trimester of pregnancy. Taurine reduced the quantity of resorption, increased the weight of placentas and fetuses. Along with a correction of the lactate level, pyruvate and lactate dehydrogenase activity, it was observed a decrease of creatine level in placentas. CONCLUSIONS: Obtained results allows us to recommend taurine, which has antioxidant, antihypoxic, membrane stabilizing, detoxifying, osmoregulating and diuretic effects, for the treatment of placental disorders with preeclampsia.
... The loading mass of pharmaceuticals could exceed 200 percent of the graphene-based drug nanocarrier, according to one study [151] . Second, graphene is chemically and mechanically stable [152] , which makes graphene-based nanomaterials appropriate for a variety of delivery settings. ...
... The loading mass of pharmaceuticals could exceed 200 percent of the graphene-based drug nanocarrier, according to one study [151]. Second, graphene is chemically and mechanically stable [152], which makes graphene-based nanomaterials appropriate for a variety of delivery settings. Third, despite the fact that virgin graphene and graphene oxide (GO) are harmful to cells and animals, their stability and biocompatibility can be considerably enhanced by a chemical treatment. ...
... It has been reported that uptake of GO nanomaterials by macrophages results in an inflammation response by promoting the secretion of pro-inflammatory cytokines, such as interleukin-6 (IL-6), IL-12, tumor necrosis factor-β (TNF-β), and interferon-gamma (IFN-β) [80]. Increasing evidence has demonstrated a proven dose-dependent cytotoxicity of GO nanomaterials [78,[81][82][83]. It appears that the size of the nanoparticles is a major factor that determines the toxicity of GO nanoparticles against normal cells, so that it has been reported that GO nanoparticles with a size of 430-780 nm have lower toxicity towards fibroblast cells [78,83,84]. ...
... In a size-and time-dependent manner, GO nanomaterials can cause cytotoxicity to cells and can damage whole organisms [337][338][339]. Besides, major body organs, such as liver, kidney, spleen, and heart, can be negatively affected by intravenous injection of GO nanoparticles [81,340]. Exposure of preosteoblast cells to GO nanosheets resulted in apoptosis and a decrease in cell proliferation [341]. ...
Nanotechnology is a growing field, with many potential biomedical applications of nanomedicine for the treatment of different diseases, particularly cancer, on the horizon. Graphene oxide (GO) nanoparticles can act as carbon-based nanocarriers with advantages such as a large surface area, good mechanical strength, and the capacity for surface modification. These nanostructures have been extensively used in cancer therapy for drug and gene delivery, photothermal therapy, overcoming chemotherapy resistance, and for imaging procedures. In the current review, we focus on the biological functions of GO nanoparticles as regulators of apoptosis and autophagy, the two major forms of programmed cell death. GO nanoparticles can either induce or inhibit autophagy in cancer cells, depending on the conditions. By stimulating autophagy, GO nanocarriers can promote the sensitivity of cancer cells to chemotherapy. However, by impairing autophagy flux, GO nanoparticles can reduce cell survival and enhance inflammation. Similarly, GO nanomaterials can increase ROS production and induce DNA damage, thereby sensitizing cancer cells to apoptosis. In vitro and in vivo experiments have investigated whether GO nanomaterials show any toxicity in major body organs, such as the brain, liver, spleen, and heart. Molecular pathways, such as ATG, MAPK, JNK, and Akt, can be regulated by GO nanomaterials, leading to effects on autophagy and apoptosis. These topics are discussed in this review to shed some lights towards the biomedical potential of GO nanoparticles and their biocompatibility, paving the way for their future application in clinical trials.
... The last 10 years have seen a growing interest in the medical application of CNM and particularly of GO, mostly thanks to its biocompatibility, antimicrobial properties and, regarding Mtb infection, its ability to accumulate in the lungs (Zhang et al., 2011;Park et al., 2015;Palmieri et al., 2017;. We have demonstrated that GO can entrap extracellular mycobacteria (De Assessment of GQDs' cytotoxicity on hPBMCs and on whole blood cells. ...
Introduction
The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains has underscored the urgent need for novel therapeutic approaches. Carbon-based nanomaterials, such as graphene oxide (GO), have shown potential in anti-TB activities but suffer from significant toxicity issues.
Methods
This study explores the anti-TB potential of differently functionalized graphene quantum dots (GQDs) – non-functionalized, L-GQDs, aminated (NH 2 -GQDs), and carboxylated (COOH-GQDs) – alone and in combination with standard TB drugs (isoniazid, amikacin, and linezolid). Their effects were assessed in both axenic cultures and in vitro infection models.
Results
GQDs alone did not demonstrate direct mycobactericidal effects nor trapping activity. However, the combination of NH 2 -GQDs with amikacin significantly reduced CFUs in in vitro models. NH 2 -GQDs and COOH-GQDs also enhanced the antimicrobial activity of amikacin in infected macrophages, although L-GQDs and COOH-GQDs alone showed no significant activity.
Discussion
The results suggest that specific types of GQDs, particularly NH 2 -GQDs, can enhance the efficacy of existing anti-TB drugs. These nanoparticles might serve as effective adjuvants in anti-TB therapy by boosting drug performance and reducing bacterial counts in host cells, highlighting their potential as part of advanced drug delivery systems in tuberculosis treatment. Further investigations are needed to better understand their mechanisms and optimize their use in clinical settings.
... Overall, functionalized nanosystems based on graphene materials show insignificant adverse effects on healthy cells, high selectivity, higher local therapeutic uptake and better drug biodistribution. [86][87][88][89][90][91][92][93][94][95] A promising concept would be to integrate graphene anticancer therapies with graphene imaging capabilities. For example, Raman imaging could facilitate tracking and monitoring the biodistribution and removal of the therapeutic load. ...
Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The “Technology and Innovation Roadmap” published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000–1500 nm) is a better option than NIR-I (750–1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.
... Relative weight was [2]: (organ weight/body weight on the day they were sacrificed) *100. Histopathological examination was performed using a standard laboratory procedures [36]. ...
... However, inhaled GNSs can easily penetrate the tracheobronchial airways and then travel down to the lower lung airways, where it destroys the ultrastructure and biophysical properties of the pulmonary epithelial GL layer [27,43], therefore, the first line of innate host defense [44]. GO was demonstrated to disrupt the alveolar-capillary barrier, allowing inflammatory cells to infiltrate the lungs, thus stimulating the release of pro-inflammatory cytokines, resulting in epithelioid granulomas, interstitial inflammation, and lung fibrosis [75][76][77]. GBNs caused inflammation and remained in the lung on day 90 after a single intratracheal instillation [78], and even translocated to the lung lymph nodes after inhalation [79]. ...
Graphene-based materials (GBMs) possess remarkable physiochemical properties, making them promising for diverse applications in biomedicine, agriculture, food, and industrial applications. Human and environmental exposure to GBMs is increasing at an unprecedented rate, yet there is still a knowledge gap regarding the safety of GBMs. This review summarizes the physiochemical properties of GBMs and critically examines the possible effects of GBMs, both at the level of molecular mechanism and at the level of the organism. While oxidative stress-mediated cell damage has been proposed as a primary cytotoxicity mechanism for GBMs, various in vivo biodistribution and cytotoxicity mechanisms are also highlighted. This review of the literature provides an overview of the cytotoxicity of GBMs, raising concerns about their widespread application with potential hazardous consequences on the environment and in human health.
... GO was demonstrated to disrupt the alveolar-capillary barrier, allowing inflammatory cells to infiltrate the lungs, thus stimulating the release of proinflammatory cytokines, resulting in epithelioid granulomas, interstitial inflammation, and lung fibrosis [104][105][106]. GBNPs caused inflammation and remained in the lung on day 90 after a single intratracheal instillation [107], and even translocated to the lung lymph nodes after inhalation [108]. ...
Abstract: Graphene-based nanoparticles possess remarkable physiochemical properties, making them promising for diverse applications in biomedicine, agriculture, food, and industrial applications. These nanoparticles have also been used in the fight against COVID-19. Human and environmental exposure to graphene-based nanomaterials is increasing at an unprecedented rate. However, there is still a huge knowledge gap regarding its safety in clinical applications. The topic remains controversial; although several routes of degradation exist, the cytotoxicity of graphene-based nanoparticles has been demonstrated. Various factors that can influence the cytotoxicity of graphene-based materials are discussed. This review summarizes the physiochemical properties of graphene-based materials and critically examines the possible effects of graphene-based nanoparticles on the molecular level and adverse health outcomes. While oxidative stressmediated cell damage has been proposed as a primary cytotoxicity mechanism for graphene-based materials, various in vivo biodistribution and cytotoxicity mechanisms are also highlighted. Therefore, this review of the
literature provides an overview of the cytotoxicity of GBMs and raises concerns about their widespread application with potential hazardous consequences on the environment and human health.
... The granuloma formation was observed mainly in the lung, spleen, kidney, and liver in 0.4 mg GO-injected mice. Similar results were reported by Zhang et al. [443] , where no pathological changes in the examined organs were observed when the mice were treated with 1 mg/kg body weight of GO. In addition, GO exhibited excellent biocompatibility with red blood cells. ...
Magnesium (Mg) composites reinforced with carbon-based nanomaterial (CBN) often exhibit low density, enhanced strength, good conductivity, improved wear resistance, and excellent biocompatibility when compared to current industry Mg alloys. This review aims to critically evaluate recent developments in Mg-CBN composites and is divided into five sections: First, a brief introduction to Mg-CBN composites is provided, followed by a discussion of different fabrication techniques for these composites, including powder metallurgy, casting, friction stir processing, and selective laser melting. A particular focus is on the current processing challenges, including dispersion strategies to create homogeneous Mg-CBN composites. The effect of processing on the quantifying disorder in CBNs and distinguishing different sp2 carbon materials is also highlighted. Then, the effect of CBN on various properties of Mg-CBN composites is thoroughly analyzed, and the strengthening efficiency of CNTs and graphene in the Mg matrix is examined. Finally, the potential applications of Mg-CBN composites in various industries are proposed, followed by a summary and suggestions for future research directions in the field of Mg-CBN composites.
... This internalization enables targeted delivery of therapeutic agents to the tumor site, enhancing efficacy and reducing side effects. Overall, the internalization of graphene oxide nanosheets with a sheet-shaped structure in cancer cell lines has implications for cancer diagnosis, therapy, and imaging [53][54][55]. ...
ARTICLE INFO
Keywords: Nanoparticles Nano-drug delivery Apoptosis and necrosis Cytotoxicity Confocal microscopy
ABSTRACT
Nanomaterial-based delivery platforms have indeed revolutionized drug delivery systems in recent years. These platforms, which are based on various types of nanoparticles, offer several advantages over traditional drug delivery systems. Therefore, during this work, we synthesized gold nanoparticles (GNPs) and graphene oxide (GO) as representative nanomaterials and assessed their biocompatibility and cytoplasmic localization in vitro. Structural characterization of the prepared nanoparticles was performed by using different techniques. For instance, laser diffraction spectrometry using a Nano-ZS Zetasizer was used to determine the particles size, and Zeta potential. High-resolution transmission electron microscopy (HR-TEM) were utilized to evaluate Particle sizes and morphologies of the prepared nanoparticles. Additionally, the chemical structure of the prepared nanoparticles was assessed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The effects of the different concentrations of GNPs and GO nanosheets on cell viability and proliferation were evaluated by WST-1 cell proliferation assays. Ultimately, in vitro studies were performed by confocal microscopy to characterize the cellular uptake of the prepared nanoparticles. The net results of this study suggest that both nanomaterials showed a cytoplasmic entry without penetrating the nucleus. They may be useful for slow drug release as well as photothermal and photodynamic therapy using a low-powered laser or IR radiation.
... Many publications have addressed the toxicity or biocompatibility of these carbon-based nanomaterials. Many articles describe the excellent biocompatibility of these materials (Bhattacharjee et al., 2021;Kiew et al., 2016;Pinto et al., 2013;Wang et al., 2011;Zhang et al., 2011) as well as their toxicity (Akhavan and Ghaderi, 2010;Chang et al., 2011;Ou et al., 2016;Seabra et al., 2014). The reason for this contrast in results could be the use of different types of cells or microorganisms for testing graphene-based nanomaterials. ...
Graphene oxides (GOs) and their reduced forms are often discussed both positively and negatively due to the lack of information about their chemistry and structure. This study utilized GOs with two sheet sizes that were further reduced by two reducing agents (sodium borohydride and hydrazine) to obtain two different degrees of reduction. The synthesized nanomaterials were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), elemental analysis (EA), Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy (RA) to understand their chemistry and structure. The second focus of our investigation included in vitro testing of the biocompatibility/toxicity of these materials on a model organism, the freshwater microalga Chlamydomonas reinhardtii. The effects were studied on the basis of biological endpoints complemented by biomass investigation (FTIR spectroscopy, EA, and atomic absorption spectrometry (AAS)). The results showed that the biocompatibility/toxicity of GOs is dependent on their chemistry and structure and that it is impossible to generalize the toxicity of graphene-based nanomaterials.
... It has been suggested that GFNs prepared by chemical vapor deposition cause an increase in the production of reactive oxygen species in neuronal cells, resulting in a significant increase in the apoptosis rate of neuronal cells. 128 Studies using mice as an animal model have shown that intravenous injection of GO leads to pulmonary edema, while intraperitoneal injection of GO causes massive accumulation in the liver and spleen. 125,129 GO is thought to bind to other body components, and the lungs and liver have a purifying effect on blood components, so GO is stored in large amounts in these organs. ...
Graphene-family nanomaterials (GFNs) possess mechanical stiffness, optical properties, and biocompatibility making them promising materials for biomedical applications. However, to realize the potential of graphene in biomedicine, it must overcome several challenges that arise when it enters the body's circulatory system. Current research focuses on the development of tumor-targeting devices using graphene, but GFNs accumulated in different tissues and cells through different pathways, which can cause toxic reactions leading to cell apoptosis and body dysfunction when the accumulated amount exceeds a certain limit. In addition, as a foreign substance, graphene can induce complex inflammatory reactions with immune cells and inflammatory factors, potentially enhancing or impairing the body's immune function. This review discusses the biomedical applications of graphene, the effects of graphene materials on human immune function, and the biotoxicity of graphene materials.
... The medical application of CNM, and particularly of GO, has been a hot topic in the last ten years, mostly due to its biocompatibility and antimicrobial properties [26]. When administered in vivo, GO preferentially accumulates in the lungs, prompting many to investigate its potential use as adjunctive therapy in respiratory infections such as TB [6,27,28]. However, the use of GO remains controversial mainly due to the variable cytotoxicity observed that can vary depending on the GO physico-chemical features (lateral size, impurities due to manufacturing methods, concentration and functionalization) and the experimental model used [22,29,30]. ...
Graphene Oxide has been proposed as a potential adjuvant to develop improved anti-TB treatment, thanks to its activity in entrapping mycobacteria in the extracellular compartment limiting their entry in macrophages. Indeed, when administered together with linezolid, Graphene Oxide significantly enhanced bacterial killing due to the increased production of Reactive Oxygen Species. In this work, we evaluated Graphene Oxide toxicity and its anti-mycobacterial activity on human peripheral blood mononuclear cells. Our data show that Graphene Oxide, different to what is observed in macrophages, does not support the clearance of Mycobacterium tuberculosis in human immune primary cells, probably due to the toxic effects of the nano-material on monocytes and CD4+ lymphocytes, which we measured by cytometry. These findings highlight the need to test GO and other carbon-based nanomaterials in relevant in vitro models to assess the cytotoxic activity while measuring antimicrobial potential.
... However, the toxicity of rGO remains controversial. Some previous studies have suggested that rGO exhibits dose-dependent toxicity (Zhang et al., 2011;Xu et al., 2015). To test whether rGO exhibits cell toxicity in our system, we inoculated 3T3 cells onto the membranes and measured their proliferation using an EDU proliferation kit. ...
The healthy human heart has special directional arrangement of cardiomyocytes and a unique electrical conduction system, which is critical for the maintenance of effective contractions. The precise arrangement of cardiomyocytes (CMs) along with conduction consistency between CMs is essential for enhancing the physiological accuracy of in vitro cardiac model systems. Here, we prepared aligned electrospun rGO/PLCL membranes using electrospinning technology to mimic the natural heart structure. The physical, chemical and biocompatible properties of the membranes were rigorously tested. We next assembled human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on electrospun rGO/PLCL membranes in order to construct a myocardial muscle patch. The conduction consistency of cardiomyocytes on the patches were carefully recorded. We found that cells cultivated on the electrospun rGO/PLCL fibers presented with an ordered and arranged structure, excellent mechanical properties, oxidation resistance and effective guidance. The addition of rGO was found to be beneficial for the maturation and synchronous electrical conductivity of hiPSC-CMs within the cardiac patch. This study verified the possibility of using conduction-consistent cardiac patches to enhance drug screening and disease modeling applications. Implementation of such a system could one day lead to in vivo cardiac repair applications.
... However, considering the intracellular event and cytokine profiles, the lateral dimensions played a significant role in the biological responses: the GO in micro-size induced much stronger inflammation responses while the smaller GO sheets showed better biocompatibility.As in the case of the in vitro impact, it is necessary to carefully consider many parameters, such as the morphological and physicochemical characteristics of each type and quality of samples, the surface modifications, the size, etc…, also for testing the toxicity of GO in vivo. Zhang et al.118 studied the biodistribution and biocompatibility of single layer GO sheets of 10-800 nm in Kunming mice after intravenous administration at a dose of 1 mg/kg or 10 mg/kg. The results showed that GO exhibited a good biocompatibility on red blood cell with a long blood circulation time (half-time 5.3±1.2 ...
Graphene oxide (GO) has attracted increasing interest as a prominent potential vector in gene delivery and in particular in gene silencing. The main goal of this work is to develop novel platforms to complex small interfering RNA (siRNA) molecules and to rationalize the supramolecular interactions between GO surface and the double strand RNA. The study focused first on the synthesis of GO with various oxygenated groups, subsequently chemically covalently modified with amines and polymers. Moreover, I investigated on the factors that could affect the double helix siRNA structure. Finally, the question of the thesis, « Can graphene oxide be a suitable platform for complexation of nucleic acids? » could be answered from the biological tests proving the ability of graphene derivatives as a carrier of siRNA into the cells.
... Necroptosis might provide a therapeutic advantage because faulty apoptotic pathways often contribute to therapy resistance. The serum half-life of RTX/GO may be shortened compared to that of free RTX, according to previous reports; 66,67 however, an extended serum half-life may not be necessary for the RTX/GO therapeutic effect, as RTX/ GO appears to eliminate lymphoma rapidly. Elimination of established lymphoma in the NRG hosts is unique to RTX/GO therapy. ...
The humanised anti-CD20 antibody (Ab) rituximab (RTX) has significantly improved the prognosis of B cell non-Hodgkin’s lymphomas (BNHL). However, major challenges remain: a) RTX is often used with toxic chemotherapy that not only causes serious side effects but may also compromise RTX activity and host antitumour immunity, predisposing patients to relapse; b) indolent low-grade BNHL remain largely incurable; c) a significant percentage of aggressive BNHL do not respond to RTX-based therapy; and d) a significant number of responders may eventually relapse in long-term follow-up. The data suggest that the limit in the efficacy may result from the inability of RTX to directly kill lymphoma cells. RTX primarily relies on indirect mechanisms to attack lymphoma cells, which include complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity, induction of apoptosis, and immune activation. These mechanisms could be readily compromised by various situations, such as chemotherapy. The new generation of anti-CD20 Ab have not been found to be directly cytotoxic. Cytotoxic radioactive isotope-conjugated anti-CD20 Ab appeared to be highly effective, but serious radiotoxicity prohibited their clinical application. Increasing Ab valency augments activity; a recent study has demonstrated drastic improvement in activity by non-covalently associating RTX with nanomaterial graphene oxide (GO). The multivalent Ab product RTX/GO is highly cytotoxic, capable of directly killing BNHL cells in vitro and rapidly eliminating established xenograft lymphoma in vivo in the absence of toxic chemo-agents. While further studies are needed to determine the mechanism of activity and clinical efficacy, the current data suggest a significant possibility that RTX/GO might constitute nontoxic but effective therapy for BNHL.
Recent advances in the field of drug delivery have opened new avenues for the development of novel nanodrug delivery systems (NDDS) in cancer therapy. Self-assembled nanoparticles (SANPs) based on tumor microenvironment have great advantages in improving antitumor effect, and pH-responsive SANPs prepared by the combination of pH-responsive nanomaterials and self-assembly technology can effectively improve the efficacy and reduce the systemic toxicity of antitumor drugs. In this review, we describe the characteristics of self-assembly and its driving force, the mechanism of pH-responsive NDDS, and the nanomaterials for pH-responsive SANPs type. A series of pH-responsive SANPs for tumor-targeted drug delivery are discussed, with an emphasis on the relation between structural features and theranostic performance.
The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under in-vivo condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%. Upon acute exposure to 10 mg/kg dose of ICG-tagged GO nanoflakes through intravenous route, various organs such as kidney, spleen and liver were observed, and the nanoparticles predominantly accumulated in the liver upon 24 h of exposure. Upon confirming the accumulation of these particles in liver through IVIS imaging, our next attempt was to analyse various biochemical and serum parameters. An elevation in various serum parameters such as ALT, AST, Creatinine and Bilirubin was observed. Similarly, in the case of biochemical parameters tested in liver homogenates, an increase in NO, Catalase, GSH, SOD, ROS, LPO, GR, GPx, and GST was observed. This study highlights the potential toxicological risk associated with GO exposure which must be taken into account for any risk analysis associated with GO based consumer products and the occupational hazards.
Two-dimensional (2D) materials have attracted tremendous interest ever since the isolation of atomically thin sheets of graphene in 2004 due to the specific and versatile properties of these materials. However, the increasing production and use of 2D materials necessitate a thorough evaluation of the potential impact on human health and the environment. Furthermore, harmonized test protocols are needed with which to assess the safety of 2D materials. The Graphene Flagship project (2013–2023), funded by the European Commission, addressed the identification of the possible hazard of graphene-based materials as well as emerging 2D materials including transition metal dichalcogenides, hexagonal boron nitride, and others. Additionally, so-called green chemistry approaches were explored to achieve the goal of a safe and sustainable production and use of this fascinating family of nanomaterials. The present review provides a compact survey of the findings and the lessons learned in the Graphene Flagship.
Graphene and graphene oxide have emerged as promising nanocarriers in the field of drug delivery due to their unique physicochemical properties and biocompatibility. This review provides an overview of the recent advancements in utilizing graphene and graphene oxide as nanocarriers for drug delivery applications. The review covers the synthesis and functionalization of these nanocarriers, focusing on their ability to load and release drugs effectively. Moreover, the biocompatibility and safety considerations associated with their use are explored. The various applications of graphene and graphene oxide nanocarriers in drug delivery are also discussed, highlighting their potential in revolutionizing targeted therapies and improving therapeutic outcomes. It would highlight the unique properties of these nanomaterials, such as their high surface area, biocompatibility and ability to be functionalized, which make them promising candidates for drug delivery applications. The abstract would summarize key findings regarding the efficiency, targeted delivery capability, and safety profile of graphene-based nanocarriers, emphasizing their potential to revolutionize drug delivery systems and improve therapeutic outcomes.
Citation: Keremidarska-Markova, M.; Sazdova, I.; Ilieva, B.; Mishonova, M.; Shkodrova, M.; Hristova-Panusheva, K.; Krasteva, N.; Chichova, M. Abstract: The growing interest in graphene oxide (GO) for different biomedical applications requires thoroughly examining its safety. Therefore, there is an urgent need for reliable data on how GO nanoparticles affect healthy cells and organs. In the current work, we adopted a comprehensive approach to assess the influence of GO and its polyethylene glycol-modified form (GO-PEG) under near-infrared (NIR) exposure on several biological aspects. We evaluated the contractility of isolated frog hearts, the activity of two rat liver enzymes-mitochondrial ATPase and diamine oxidase (DAO), and the production of reactive oxygen species (ROS) in C2C12 skeletal muscle cells following direct exposure to GO nanoparticles. The aim was to study the influence of GO nanoparticles at multiple levels-organ; cellular; and subcellular-to provide a broader understanding of their effects. Our data demonstrated that GO and GO-PEG negatively affect heart contractility in frogs, inducing stronger arrhythmic contractions. They increased ROS production in C2C12 myoblasts, whose effects diminished after NIR irradiation. Both nanoparticles in the rat liver significantly stimulated DAO activity, with amplification of this effect after NIR irradiation. GO did not uncouple intact rat liver mitochondria but caused a concentration-dependent decline in ATPase activity in freeze/thaw mitochondria. This multifaceted investigation provides crucial insights into GOs potential for diverse implications in biological systems.
: Graphene oxide - potential use in wood protection based on a review of antibacterial and fungicide properties. Graphene oxide is a material that has been generating interest among researchers in recent years. Due to its properties, it can be used in many scientific and industrial fields. Not all of its properties are significantly known, making it a potential subject of research in many different aspects. The topic of this article is to assess the potential applications of graphene oxide in the field of wood science industry. Based on the literature, the antibacterial and fungicidal properties are characterised. The fungicidal effect of graphene oxide, mainly in plant protection, leads to consideration of the potential use of this material in protection against wood-destroying fungi.
Nanoparticles have shown significant potential in dental implants as they have distinctive properties and potential benefits. They have distinct physicochemical features that differ from their bulk equivalents. These characteristics make nanoparticles highly appealing for application in commercial and medical research. The main objective of nanotechnology research and development is to advance overarching social goals, including enhancing human potential and pushing the limits of environmentally sound growth. Considering this, graphene nanoparticles are rapidly overtaking other nanostructures as the favoured option for contemporary biomedical applications. This paper reviews the significance of nanoparticles in various fields and critically examines the importance of graphene nanoparticles in dental implant applications. It also discusses techniques for graphene synthesization and characterization. Additionally, it featured multiple applications of graphene in dental implants along with the present difficulties and potential outcomes. Numerous potential applications in dentistry research exist for this highly adaptable nanotechnology. Due to its distinctive characteristics and possible advantages , graphene nanoparticles have demonstrated promise in dental implants.
Multidrug-resistant (MDR) bacteria-caused infections have been a major threat to human health. The abuse of conventional antibiotics accelerates the generation of MDR bacteria and makes the situation worse. The emergence of nanomaterials holds great promise for solving this tricky problem due to their multiple antibacterial mechanisms, tunable antibacterial spectra, and low probabilities of inducing drug resistance. In this review, we summarize the mechanism of the generation of drug resistance, and introduce the recently developed nanomaterials for dealing with MDR bacteria via various antibacterial mechanisms. Considering that biosafety and mass production are the major bottlenecks hurdling the commercialization of nanoantibiotics, we introduce the related development in these two aspects. We discuss urgent challenges in this field and future perspectives to promote the development and translation of nanoantibiotics as alternatives against MDR pathogens to traditional antibiotics-based approaches.
Graphene, fullerenes, diamond, carbon nanotubes, and carbon dots are just a few of the carbon-based nanomaterials that have gained enormous popularity in a variety of scientific disciplines and industrial uses. As a two-dimensional material in the creation of therapeutic delivery systems for many illnesses, nanosized graphene oxide (NGO) is now garnering a large amount of attention among these materials. In addition to other benefits, NGO functions as a drug nanocarrier with remarkable biocompatibility, high pharmaceutical loading capacity, controlled drug release capability, biological imaging efficiency, multifunctional nanoplatform properties, and the power to increase the therapeutic efficacy of loaded agents. Thus, NGO is a perfect nanoplatform for the development of drug delivery systems (DDSs) to both detect and treat a variety of ailments. This review article’s main focus is on investigating surface functionality, drug-loading methods, and drug release patterns designed particularly for smart delivery systems. The paper also examines the relevance of using NGOs to build DDSs and considers prospective uses in the treatment of diseases including cancer, infection by bacteria, and bone regeneration medicine. These factors cover the use of naturally occurring medicinal substances produced from plant-based sources.
Introduction:
Graphene-based materials (GBMs) have unique physicochemical properties that make them extremely attractive as platforms for the design of new drugs. Indeed, their bidimensional (2D) morphology, high surface area, mechanical and optical properties, associated to different possibilities for functionalization of their surface, provides opportunities for their use as nanomedicines for drug delivery and/or phototherapies.
Areas covered:
This opinion paper provides an overview of the current status of GBMs in drug design, with a focus on their therapeutic applications, potential environmental and health risks, and some controversial results. The authors discuss the chemical modifications of GBMs for the treatment of various diseases. The potential toxicity associated with some GBMs is also presented, along with a safe-by-design approach to minimize the risks. Finally, the authors address some issues associated to the use of GBMs in the biomedical field, such as contradictory antibacterial effects, fluorescence quenching and imprecise chemical functionalization.
Expert opinion:
GBMs are a promising and exciting area of research in drug delivery. It is however important that responsible and safe use of these materials is ensured to fully exploit their advantages and overcome their drawbacks.
Polymer gels are an important class of soft materials with growing interest for biomedical applications due to their distinctive properties. These three‐dimensional polymer networks are capable of imbibing large amounts of solvent while maintaining solid‐like behavior. Polymer gels can be classified into hydrogels, aerogels, and cryogels based on their structural features. Their highly porous structure, swelling capacity, and biocompatibility make them well‐suited for diverse uses in biomedicine. Recent advances have enabled the engineering of polymer gels with tunable architectures and smart functionality responsive to stimuli. These developments have expanded the potential of gels in areas like tissue engineering, drug delivery, wound healing, and biosensing. However, the toxicity of polymer gels remains an important consideration for biomedical use. Careful design and toxicological evaluation is essential to ensure safe clinical application. Overall, polymer gels offer new possibilities in biomedicine through continued research on synthesizing biocompatible gels and elucidating structure–function relationships. This review provides an updated perspective on the progress and promise of tailoring polymer gels to advance biomedicine, while also considering the critical aspect of biocompatibility.
Hydrogen production by photoelectrochemical (PEC) water splitting has attracted considerable interest because it is a promising clean source of energy for improving the earth’s climate in the future. Owing to the excellent properties of graphene, the use of graphene in photocatalysis for green hydrogen production has attracted remarkable interest. 3D graphene, which can act as a co-catalyst and transfer agent to enhance photocatalytic hydrogen production, is a potential component for PEC electrodes due to its substantial surface area, fast electron transfer, high electron conductivity, low mass density, mechanical stability, interconnected and hierarchical structure. The use of 3D-graphene-based photocatalysts in PEC water-splitting applications is highlighted and discussed in this chapter. Various strategies and approaches for the synthesis of 3D graphene are also presented. Efforts have been made in the incorporation of 3D graphene with metal oxides, transition-metal dichalcogenides (TMDCs), or other semiconductor materials wherein the synergistic effect between these materials can suppress the recombination of photogenerated electron–hole pairs to enhance PEC water-splitting performance considerably. This chapter presents an inclusive review of the photocatalytic characteristics and current development of 3D graphene-based photocatalysts for water-splitting applications.Keywords3D graphenePhotocatalystsPhotoelectrochemical water splittingHydrogen production
As the production of graphene has increased and its range of uses has expanded, worries about the possible harmful effects that its derivative nanoparticles and materials may have on human health have come to the fore. Numerous studies have demonstrated that graphene, in whatever shape it takes, affects a wide range of living things. Prokaryotic bacteria, viruses, plants, micro- and macro-invertebrates, mammalian and human cells, and whole creatures in vivo are some of these organisms. However, there is frequently a great deal of disagreement, if not outright controversy, regarding the results of the studies that have been carried out. As a result, we present in this paper a critical analysis of the most recent reports that have been gathered in the area of the biocompatibility and toxicology of materials related to graphene. Our objective is to provide information on the most current developments, new trends, and potential career opportunities in this area. Graphene exposure scenarios like inhalation through the respiratory system, ingestion through the digestive tract, administration via the parenteral route, and topical exposure through the skin are examined in the context of the experiment results using a variety of in vitro and in vivo model systems.KeywordsGrapheneGraphene derivativesHealthEnvironmentCytotoxicity
At present, cancer remains one of the leading causes of human death worldwide, and surgery, radiotherapy and chemotherapy are still the main methods of cancer treatment. However, these treatments have their drawbacks. Surgical treatment often struggles with the complete removal of tumor tissue, leading to a high risk of cancer recurrence. Additionally, chemotherapy drugs have a significant impact on overall health and can easily result in drug resistance. The high risk and mortality of cancer and other reasons promote scientific researchers to unremittingly develop and find a more accurate and faster diagnosis strategy and effective cancer treatment method. Photothermal therapy, which utilizes near-infrared light, offers deeper tissue penetration and minimal damage to surrounding healthy tissues. Compared to conventional radiotherapy and other treatment methods, photothermal therapy boasts several advantages, including high efficiency, non-invasiveness, simplicity, minimal toxicity, and fewer side effects. Photothermal nanomaterials can be categorized as either organic or inorganic materials. This review primarily focuses on the behavior of carbon materials as inorganic materials and their role in tumor photothermal treatment. Furthermore, the challenges faced by carbon materials in photothermal treatment are discussed.
Bacterial infections pose a significant threat to human health and a heavy burden on the global healthcare system. Antibiotics are the primary treatment, but they can lead to bacterial resistance and adverse side effects. Two-dimensional (2D) nanomaterials such as graphene, MoS2, and MXene have emerged as novel antibacterial agents due to their potential to circumvent bacterial resistance. Among the 2D nanomaterials, black phosphorus nanosheets (BPNs) have attracted great research interest due to their excellent biocompatibility. BPNs possess unique properties, such as a high specific surface area, tunable bandgap, and easy surface functionalization, enabling them to combat bacteria through physical disruption of bacterial membranes, photothermal and photodynamic therapies. However, the low preparation efficiency and inevitable oxidative degradation of BPNs have limited their wide application. This review provides a comprehensive overview of recent advances in antibacterial research on BPNs, encompassing their preparation methods, structural and physicochemical properties, antibacterial mechanisms, and potential applications. By addressing the challenges and prospects of using BPNs as an alternative to antibiotics, this review provides valuable insights and guidance for utilizing BPNs in shaping the future of antibacterial therapy.
The review is a continuation of the previously published one on the toxicity of spherical nanostructures of carbon, namely fullerenes and nanoonions. This review considers data on the toxicity of carbon nanostructures in sp2-hybridization of carbon atoms, which can be considered as formed from graphene sheets, and nanostructures formed by carbon atoms in sp3-hybridization, namely, nanodiamonds. Unfortunately, it should be repeated the conclusion made in the previous review that at the moment there is not enough data to use carbon nanostructures in practice, and therefore it is necessary to develop more effective and informative tests on animals, taking into account the characteristics of each type of nanomaterials.
The review is a continuation of the previously published one on the toxicity of spherical nanostructures of carbon, namely fullerenes and nanoonions. This review considers data on the toxicity of carbon nanostructures in sp2-hybridization of carbon atoms, which can be considered as formed from graphene sheets, and nanostructures formed by carbon atoms in sp3-hybridization, namely, nanodiamonds. Unfortunately, it should be repeated the conclusion made in the previous review that at the moment there is not enough data to use carbon nanostructures in practice, and therefore it is necessary to develop more effective and informative tests on animals, taking into account the characteristics of each type of nanomaterials.
Graphene is a super-carbon-allotrope which has found unprecedented applications in medicine, especially in areas such as drug-containment and delivery, due to its attainment of uniquely induced properties when doped with nanoparticles. In theranostics, graphene aids the destruction of cancerous cells toward improving the tendencies for human survival. Also, the diagnostic-accuracy of combining magnetometer-aided sentinel lymphadenectomy, with intraprostatic injection of superparamagnetic iron oxide nanoparticles supported on graphene, holds high prospects for controlling intermediate/high-risk prostate cancer. There are also evidences of the efficacy of the combined use of sonodynamic therapy with anticancer micelles supported on graphene, as well as high-intensity ultrasound for the treatment of canine cancer after diagnosis. Furthermore, superparamagnetic oxygenated nanobubbles impregnated in graphene are proven enhancers for the oxygenation of tumors during hyperthermia. Therefore, this chapter entails discussions on recent advances on the use of graphene-based nanocomposites in theranostic applications.
Research on graphene based nanomaterials has flourished in the last decade due their unique properties and emerging socio-economic impact. In the context of their potential exploitation for biomedical applications, there is a growing need for the development of more efficient imaging techniques to track the fate of these materials. Herein we propose the first correlative imaging approach based on the combination of radioimaging and mass spectrometry imaging for the detection of Graphene Oxide (GO) labelled with carbon-14 in mice. In this study, 14C-graphene oxide nanoribbons were produced from the oxidative opening of 14C-carbon nanotubes, and were then intensively sonicated to provide nano-size 14C-GO flakes. After Intravenous administration in mice, 14C-GO distribution was quantified by radioimaging performed on tissue slices. On the same slices, MS-imaging provided a highly resolved distribution map of the nanomaterial based on the detection of specific radical anionic carbon clusters ranging from C2˙- to C9˙- with a base peak at m/z 72 (12C) and 74 (14C) under negative laser desorption ionization mass spectrometry (LDI-MS) conditions. This proof of concept approach synergizes the strength of each technique and could be advantageous in the pre-clinical development of future Graphene-based biomedical applications.
Nerve guidance conduits (NGCs) have become a promising alternative for peripheral nerve regeneration; however, the outcome of nerve regeneration and functional recovery is greatly affected by the physical, chemical, and electrical properties of NGCs. In this study, a conductive multiscale filled NGC (MF‐NGC) consisting of electrospun poly(lactide‐co‐caprolactone) (PCL)/collagen nanofibers as the sheath, reduced graphene oxide /PCL microfibers as the backbone, and PCL microfibers as the internal structure for peripheral nerve regeneration is developed. The printed MF‐NGCs presented good permeability, mechanical stability, and electrical conductivity, which further promoted the elongation and growth of Schwann cells and neurite outgrowth of PC12 neuronal cells. Animal studies using a rat sciatic nerve injury model reveal that the MF‐NGCs promote neovascularization and M2 transition through the rapid recruitment of vascular cells and macrophages. Histological and functional assessments of the regenerated nerves confirm that the conductive MF‐NGCs significantly enhance peripheral nerve regeneration, as indicated by improved axon myelination, muscle weight increase, and sciatic nerve function index. This study demonstrates the feasibility of using 3D‐printed conductive MF‐NGCs with hierarchically oriented fibers as functional conduits that can significantly enhance peripheral nerve regeneration. A conductive multiscale nerve guidance conduit is employed in treating peripheral nerve injuries by integrating multiscale and multifunctional biomaterials with advanced 3D printing. The printed nerve guidance conduit promotes the growth of neuronal cells, facilitates neovascularization and M2 transition of macrophages, ultimately enhancing peripheral nerve regeneration and providing an innovative clinical treatment strategy from the tissue‐engineering perspective.
The objective of this manuscript is to provide quantitative insights into the tissue distribution of nanoparticles. Published pharmacokinetics of nanoparticles in plasma, tumor and 13 different tissues of mice were collected from literature. A total of 2018 datasets were analyzed and biodistribution of graphene oxide, lipid, polymeric, silica, iron oxide and gold nanoparticles in different tissues was quantitatively characterized using Nanoparticle Biodistribution Coefficients (NBC). It was observed that typically after intravenous administration most of the nanoparticles are accumulated in the liver (NBC=17.56 %ID/g) and spleen (NBC=12.1 %ID/g), while other tissues received less than 5 %ID/g. NBC values for kidney, lungs, heart, bones, brain, stomach, intestine, pancreas, skin, muscle and tumor were found to be 3.1 %ID/g, 2.8 %ID/g, 1.8 %ID/g, 0.9%ID/g, 0.3%ID/g, 1.2%ID/g, 1.8 %ID/g, 1.2%ID/g, 1.0%ID/g, 0.6%ID/g and 3.4 %ID/g, respectively. Significant variability in nanoparticle distribution was observed in certain organs such as liver, spleen and lungs. A large fraction of this variability could be explained by accounting for the differences in nanoparticle physicochemical properties such as size and material. A critical overview of published nanoparticle physiologically-based pharmacokinetic (PBPK) models is provided, and limitations in our current knowledge about in vitro and in vivo pharmacokinetics of nanoparticles that restrict the development of robust PPBK models is also discussed. It is hypothesized that robust quantitative assessment of whole-body pharmacokinetics of nanoparticles and development of mathematical models that can predict their disposition can improve the probability of successful clinical translation of these modalities.
Since its discovery in 2004, graphene is increasingly applied in various fields owing to its unique properties. Graphene application in the biomedical domain is promising and intriguing as an emerging 2D material with a high surface area, good mechanical properties, and unrivalled electronic and physical properties. This review summarizes six typical synthesis methods to fabricate pristine graphene (p‐G), graphene oxide (GO), and reduced graphene oxide (rGO), followed by characterization techniques to examine the obtained graphene materials. As bare graphene is generally undesirable in vivo and in vitro, functionalization methods to reduce toxicity, increase biocompatibility, and provide more functionalities are demonstrated. Subsequently, in vivo and in vitro behaviors of various bare and functionalized graphene materials are discussed to evaluate the functionalization effects. Reasonable control of dose (<20 mg kg⁻¹), sizes (50–1000 nm), and functionalization methods for in vivo application are advantageous. Then, the key biomedical applications based on graphene materials are discussed, coupled with the current challenges and outlooks of this growing field. In a broader sense, this review provides a comprehensive discussion on the synthesis, characterization, functionalization, evaluation, and application of p‐G, GO, and rGO in the biomedical field, highlighting their recent advances and potential.
La vectorisation de médicaments, qui permet de les acheminer sur les tissus cibles pour accroitre leur activité pharmacologique tout en limitant leur toxicité et effets indésirables, est un axe de recherche en forte expansion dans lequel les nanotechnologies sont un des facteurs clés. L’un des enjeux dans cette thèse a donc été de développer une méthode d’imagerie combinée entre la MSI et l’imagerie β pour l’étude de la biodistribution de nanoparticules de type graphène. Malgré l’étude de nanoparticules hétérogènes, les analyses ont permis de déterminer une signature carbonée répétable de l’oxyde de graphène en analyse LDI - MS et ainsi que des analyses reproductibles de MSI avec de CV inférieur à 30 %. De plus, la combinaison des deux techniques a permis d’obtenir la quantification absolue du GO en radioimagerie après exposition de souris à trois doses d’injection ainsi que la biodistribution à 25 µm de résolution spatiale de ces nanoparticules au sein des tissus grâce à l’apport de la MSI. Lors d’un second projet concernant l’étude de vecteurs micellaires polymériques encapsulant un médicament, une méthode MALDI - TOF a également été développée afin de détecter ces deux molécules simultanément. Cependant, les expérimentations réalisées ont montré le besoin de développer des protocoles de traitements tissulaire compatibles avec la MSI et permettant d’améliorer le seuil de sensibilité de cette technique analytique.
Graphdiyne (GDY) is a novel two-dimensional (2D) carbon allotrope that has attracted much attention in materials, physics, chemistry, and microelectronics for its excellent properties. Much effort has been devoted to exploring the biomedical applications of GDY in 2D carbon nanomaterials, especially for smart drugs and gene delivery. However, few studies have focused on the biocompatibility and potential environmental hazards of GDY and its derivatives. In this study, graphdiyne oxide (GDYO) and graphene oxide (GO) were obtained using different oxidation methods. Their cytotoxicity and hemolysis in vitro and biocompatibility in subcutaneous and peritoneal locations in vivo were compared. GDYO had very low biotoxicity in vitro and was moderately biocompatible in the muscle and abdominal cavity in vivo. Highly oxidized products and graphdiyne quantum dots (GDQDs) were observed in peritoneal cells. GDYO had better biocompatibility and its sheet size was easily diminished through oxidative degradation. Therefore, GDYO is a good candidate for use in 2D carbon nanomaterials in biomedicine.
Single-walled carbon nanotubes (SWNTs) exhibit unique size, shape and physical properties1, 2, 3 that make them promising candidates for biological applications. Here, we investigate the biodistribution of radio-labelled SWNTs in mice by in vivo positron emission tomography (PET), ex vivo biodistribution and Raman spectroscopy. It is found that SWNTs that are functionalized with phospholipids bearing polyethylene-glycol (PEG) are surprisingly stable in vivo. The effect of PEG chain length on the biodistribution and circulation of the SWNTs is studied. Effectively PEGylated SWNTs exhibit relatively long blood circulation times and low uptake by the reticuloendothelial system (RES). Efficient targeting of integrin positive tumour in mice is achieved with SWNTs coated with PEG chains linked to an arginine–glycine–aspartic acid (RGD) peptide. A high tumour accumulation is attributed to the multivalent effect of the SWNTs. The Raman signatures of SWNTs are used to directly probe the presence of nanotubes in mice tissues and confirm the radio-label-based results.
A superparamagnetic graphene oxide –Fe 3 O 4 nanoparticles hybrid (GO–Fe 3 O 4) was prepared via a simple and effective chemical precipitation method. The amount of loading of Fe 3 O 4 on GO was estimated as 18.6 wt% by atomic absorption spectrometry. The hybrid was then loaded with doxorubicin hydrochloride (DXR) and the loading capacity was as high as 1.08 mg mg À1 . Both of the GO–Fe 3 O 4 hybrids before and after loading with DXR can be dispersed well in aqueous solution. They can congregate under acidic conditions and move regularly under the force of an external magnet. Furthermore, the aggregated hybrid can be redispersed to form a stable suspension under basic conditions. These properties make it a potential candidate for controlled targeted drug delivery and release.
Several nanometer-thick graphene oxide films deposited on silicon nitride-on silicon substrates were exposed to nine different heat treatments (three in Argon, three in Argon and Hydrogen, and three in ultra-high vacuum), and also a film was held at 70 °C while being exposed to a vapor from hydrazine monohydrate. The films were characterized with atomic force microscopy to obtain local thickness and variation in thickness over extended regions. X-ray photoelectron spectroscopy was used to measure significant reduction of the oxygen content of the films; heating in ultra-high vacuum was particularly effective. The overtone region of the Raman spectrum was used, for the first time, to provide a “fingerprint” of changing oxygen content.
We have proved that functionalized nanoscale graphene oxide can protect oligonucleotides from enzymatic cleavage and efficiently deliver oligonucleotides into cells.
Two-dimensional graphene offers interesting electronic, thermal, and mechanical properties that are currently being explored for advanced electronics, membranes, and composites. Here we synthesize and explore the biological applications of nano-graphene oxide (NGO), i.e., single-layer graphene oxide sheets down to a few nanometers in lateral width. We develop functionalization chemistry in order to impart solubility and compatibility of NGO in biological environments. We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration. The NGO sheets are found to be photoluminescent in the visible and infrared regions. The intrinsic photoluminescence (PL) of NGO is used for live cell imaging in the near-infrared (NIR) with little background. We found that simple physisorption via pi-stacking can be used for loading doxorubicin, a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro. Owing to its small size, intrinsic optical properties, large specific surface area, low cost, and useful non-covalent interactions with aromatic drug molecules, NGO is a promising new material for biological and medical applications.
Carbon nanotubes are promising for use in biomedical and pharmaceutical sciences. Therefore, it becomes imperative to know the basic biological properties of carbon nanotubes in vivo. We labeled the water-soluble hydroxylated carbon single-wall nanotubes with radioactive 125I atoms, and then the tracer was used to study the distribution of hydroxylated carbon single-wall nanotubes in mice. They moved easily among the compartments and tissues of the body, behaving as small active molecules though their apparent mean molecular weight is tremendously large. This study, for the first time, affords a quantitative analysis of carbon nanotubes accumulated in animal tissues.
Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ((111)In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.
Graphene sheets--one-atom-thick two-dimensional layers of sp2-bonded carbon--are predicted to have a range of unusual properties. Their thermal conductivity and mechanical stiffness may rival the remarkable in-plane values for graphite (approximately 3,000 W m(-1) K(-1) and 1,060 GPa, respectively); their fracture strength should be comparable to that of carbon nanotubes for similar types of defects; and recent studies have shown that individual graphene sheets have extraordinary electronic transport properties. One possible route to harnessing these properties for applications would be to incorporate graphene sheets in a composite material. The manufacturing of such composites requires not only that graphene sheets be produced on a sufficient scale but that they also be incorporated, and homogeneously distributed, into various matrices. Graphite, inexpensive and available in large quantity, unfortunately does not readily exfoliate to yield individual graphene sheets. Here we present a general approach for the preparation of graphene-polymer composites via complete exfoliation of graphite and molecular-level dispersion of individual, chemically modified graphene sheets within polymer hosts. A polystyrene-graphene composite formed by this route exhibits a percolation threshold of approximately 0.1 volume per cent for room-temperature electrical conductivity, the lowest reported value for any carbon-based composite except for those involving carbon nanotubes; at only 1 volume per cent, this composite has a conductivity of approximately 0.1 S m(-1), sufficient for many electrical applications. Our bottom-up chemical approach of tuning the graphene sheet properties provides a path to a broad new class of graphene-based materials and their use in a variety of applications.
Multiwalled carbon nanotubes (MWNTs) made highly water-dispersible by organic functionalization and radiolabeled with Indium-111 were shown to translocate through the kidney glomerular filter. On p. 225, multinational, multicenter research led by Kostas Kostarelos on dynamic imaging and tissue distribution of MWNTs in live animals is presented. The cover image presents a single plane single photon computed tomography whole body image of a rat following intravenous injection with the In-111 labeled MWNTs as seen through a 3D carbon NT projection. The radioactivity from carbon NTs was mainly localized in the kidneys, and accumulated in the bladder before clearance in the urine.
In this work, we relate the self-diffusion coefficient to the residual entropy of the system according to the free volume theory and scaling principle. The viscosity equation for a freely jointed Lennard-Jones chain fluid is then obtained from the expression of self-diffusion coefficient by applying the Stokes–Einstein equation. The real polyatomic compounds are modeled as chains of tangent Lennard-Jones segments. The segment size and energy parameter as well as chain length (expressed by the number of segments) are obtained from the experimental viscosity data. The proposed viscosity equation reproduces the experimental viscosity data with an average absolute deviation of 5.12% for 18 polyatomic compounds (1600 data points) over wide ranges of temperature and pressure. For engineering applications, the generalized model parameters for normal alkanes with the number of carbon atoms n>3 are proposed. The segment energy parameter is suggested to be evaluated from the critical temperature, and the segment size parameter and chain length are correlated with the number of carbon atoms in an alkane molecule.
A direct electrochemical method to reduce single-layer graphene oxide (GO) adsorbed on the 3-aminopropyltriethoxysilane (APTES)-modified conductive electrodes is proposed. The reduced GO adsorbed on glassy carbon electrode was modified with glucose oxidase (GOx) by covalent bonding via a polymer generated by electrografting N-succinimidyl acrylate (NSA). The direct electron transfer between the electrode and GOx molecules was realized. The bioactivity of GOx maintains very well on the electrode. The thus-prepared GOx-modified electrode was successfully used to detect glucose.
Graphene oxide platelets synthesized by using a chemical exfoliation method were deposited on anatase TiO2 thin films. Postannealing of the graphene oxide/TiO2 thin films at 400 °C in air resulted in partial formation of a Ti−C bond between the platelets and their beneath thin film. By using atomic force microscopy and X-ray photoelectron spectroscopy analyses, UV−visible light-induced photocatalytic reduction of the graphene oxide platelets of the annealed graphene oxide/TiO2 thin films immersed in ethanol was studied for the different irradiation times. After 4 h of photocatalytic reduction, the vertical space between the platelets decreased from about 1.1 to less than 0.8 nm and the concentration of the C═O bond was reduced 85%, indicating effective reduction of the graphene oxide platelets to the graphene ones. The graphene oxide/TiO2 thin films reduced at different irradiation times were utilized as nanocomposite photocatalysts for degradation of E. coli bacteria in an aqueous solution under solar light irradiation. The photocatalytic reduction of the graphene oxide platelets for 4 h caused an improvement of the antibacterial activity of the TiO2 thin film by a factor of about 7.5. The reduced graphene oxide platelets were chemically stable after photoinactivation of the bacteria.
A straightforward one-step chemical method to in situ synthesis of Ag nanoparticles (Ag NPs) on single-layer graphene oxide (GO) and reduced graphene oxide (r-GO) surfaces is proposed. After simply heating the single-layer GO or r-GO adsorbed on 3-aminopropyltriethoxysilane (APTES)-modified Si/SiOx substrates in a silver nitrate aqueous solution at 75 °C, Ag NPs are synthesized and grow on the GO or r-GO surface. The obtained Ag NPs are investigated by atomic force microscopy, scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and Raman spectroscopy. Our method is unique and important since no reducing agent is required in the reaction. Au NPs on a GO surface are obtained by simply immersing the obtained Ag NPs on the GO surface in HAuCl4 solution.
The biodistribution of pristine single-walled carbon nanotubes (SWNTs) in mice was determined by using the skeleton 13C-enriched SWNTs and isotope ratio mass spectroscopy. The results suggested that the SWNTs were distributed in the entire body, with major accumulations in the liver, lungs, and spleen over an extended period of time. The specimen from the effected organ tissues were examined by using transmission electron microscopy, aimed toward an understanding of the possible uptake mechanism. The biological consequence of pristine SWNTs is obviously very different from that of their chemically modified or functionalized counterparts. The implication of such a fact is discussed.
Coupling nanomaterials with biomolecular recognition events represents a new direction in nanotechnology toward the development of novel molecular diagnostic tools. Here a graphene oxide (GO)-based multicolor fluorescent DNA nanoprobe that allows rapid, sensitive, and selective detection of DNA targets in homogeneous solution by exploiting interactions between GO and DNA molecules is reported. Because of the extraordinarily high quenching efficiency of GO, the fluorescent ssDNA probe exhibits minimal background fluorescence, while strong emission is observed when it forms a double helix with the specific targets, leading to a high signal-to-background ratio. Importantly, the large planar surface of GO allows simultaneous quenching of multiple DNA probes labeled with different dyes, leading to a multicolor sensor for the detection of multiple DNA targets in the same solution. It is also demonstrated that this GO-based sensing platform is suitable for the detection of a range of analytes when complemented with the use of functional DNA structures.
Nanodiamond (ND) is highly expected to become a versatile material for biological applications, such as biosensors, drug carriers, and imaging probes. Understanding the basic biological consequence of ND is crucial for realizing its biorelevant applications and ascertaining its possible hazards to organisms. In this work, we found that NDs with a diameter of around 50 nm predominantly accumulated in liver after intravenous injection to mouse. Spleen and lung were also target organs for NDs. Analysis of the digested solution of liver and lung by spectroscopic method shows that about 60% of initial NDs were entrapped in liver at 0.5 h post dosing and 8% in lung. The values remained the same at 28 days post injection. The high-resolution transmission electron micrographic imaging and the Raman spectrum of the digested organ solutions confirmed the long-term entrapment of NDs in mouse liver and lung. The NDs were barely detectable in urine and feces by Raman measurement. Considering quite a number of NDs remain in the important organs, potential toxicity study is urgently needed.
The soluble bacterial epoxide hydrolase (EH) from Sphingomonas sp. HXN-200 catalyzed the enantioselective hydrolysis of racemic styrene oxide to give (S)-styrene oxide with an enantiomeric ratio (E) of 21–23 in aqueous buffer, better than any reported native EHs. The ring opening of the styrene oxide with this EH was only at the terminal position for the (S)-enantiomer and at the terminal and benzylic position in an 87:13 ratio for the (R)-enantiomer. Enzymatic hydrolysis of the styrene oxide in a two-liquid phase system significantly reduced autohydrolysis, thus improving the E to 26–29. Hydrolysis of 160mM styrene oxide with cell-free extract (CFE) of Sphingomonas sp. HXN-200 (10mg protein/mL) in aqueous buffer and n-hexane (1:1) for 30.7h afforded 39.2% (62.7mM) of (S)-styrene oxide in >99.9% ee. The lyophilized CFE was proven to be stable, while the rehydrated lyophilized CFE powder was successfully used for the hydrolysis of 320mM styrene oxide in the two-liquid phase system, yielding 40.2% (128.6mM) of (S)-styrene oxide in >99.9% ee after 13.8h. No inhibitory effect of the diol product on the hydrolysis was observed when the diol concentration was lower than 476mM, suggesting a straightforward process for the hydrolysis of up to 1M styrene oxide.
A novel graphene oxide-doxorubicin hydrochloride nanohybrid (GO-DXR) was prepared via a simple noncovalent method, and the loading and release behaviors of DXR on GO were investigated. An efficient loading of DXR on GO as high as 2.35 mg/mg was obtained at the initial DXR concentration of 0.47 mg/mL. The loading and release of DXR on GO showed strong pH dependence, which may be due to the hydrogen-bonding interaction between GO and DXR. The fluorescent spectrum and electrochemical results indicate that strong π-π stacking interaction exists between them.
Multi-walled carbon nanotubes functionalized with diethylentriaminepentaacetic dianhydride (DTPA-MWNT) and radiolabeled with Indium-111, having therapeutic and diagnostic applications, were tracked in the systemic blood circulation and the excretory system using a microSingle Photon Emission Tomography (microSPECT) scanner. Quantitative Kaiser test was used to determine the number of free amino groups on the DTPA-MWNT. A suspension of PBS and DTPA-MWNT was intravenously injected by tail vein in the Wistar rats and the urine production, water consumption and body weight were observed for 24 hours. The rat was necropised and tissues of various organs were fixed and observed with a Nikon Microphot-FXA microscope coupled with digital camera. The Length of DTPA-MWNT used in the study is larger than the dimensions of the glomerular capillary wall, so it was excreted through urine after 24 hours post-administration.
Despite great recent progress with carbon nanotubes and other nanoscale fillers, the development of strong, durable, and cost-efficient multifunctional nanocomposite materials has yet to be achieved. The challenges are to achieve molecule-level dispersion and maximum interfacial interaction between the nanofiller and the matrix at low loading. Here, the preparation of poly(vinyl alcohol) (PVA) nanocomposites with graphene oxide (GO) using a simple water solution processing method is reported. Efficient load transfer is found between the nanofiller graphene and matrix PVA and the mechanical properties of the graphene-based nanocomposite with molecule-level dispersion are significantly improved. A 76% increase in tensile strength and a 62% improvement of Young's modulus are achieved by addition of only 0.7 wt% of GO. The experimentally determined Young's modulus is in excellent agreement with theoretical simulation.
Radiolabeling of fullerol, 125I–C60(OH)x
, was performed by the traditional chloramine-T method. The C–I covalent bond in I–C60(OH)x
was characterized by X-ray photoelectron spectroscopy (XPS) that was sufficiently stable for in vivo study. Laser light scattering spectroscopy clearly showed that C60(OH)x
aggregated to large nanoparticle clumps with a wide range of distribution. The clumps formed were also visualized by transmission electron microscope (TEM). We examined the biodistribution and tumor uptake of C60(OH)x
in five mouse bearing tumor models, including mouse H22 hepatocarcinoma, human lung giantcellcarcinoma PD, human colon cancer HCT-8, human gastric cancer MGC803, and human OS732 osteosarcoma. The accumulation ratios of 125I–C60(OH)x
in mouse H22 hepatocarcinoma to that in normal muscle tissue (T/N) and blood (T/B) at 1, 6, 24 and 72 h, reveal that 125I–C60(OH)x
gradually accumulates in H22 tumor, and retains for a quite long period (e.g., T/N 3.41, T/B 3.94 at 24 h). For the other four tumor models, the T/N ratio at 24 h ranges within 1.21–6.26, while the T/B ratio ranges between 1.23 and 4.73. The accumulation of C60(OH)x
in tumor is mostly due to the enhanced permeability and retention effect (EPR) and the phagocytosis of mononuclear phagocytes. Hence, C60(OH)x
might serve as a photosensitizer in the photodynamic therapy of some kinds of tumor.
An increasing number of studies have been devoted to studying the respiratory toxicity of carbon nanomaterials, but little information is known, thus far, on the biodistribution of these nanomaterials after inhalation or intratracheal instillation. We synthesized and labeled a polyhydroxylated derivative of fullerene C60(OH)x (x = 22, 24) with 99mTc. With single photon emission computed tomography imaging and 〈gamma〉-ray counting techniques, the biodistribution of 99mTc-C60(OH)x in Sprague–Dawley rats after intratracheal instillation was studied. It was found that, besides the highest retention in the lung, 99mTc-C60(OH)x is distributed mainly in the liver, bone, and spleen, with no uptake found in brain. The long-term retention in the lung and the very fast clearance from the blood revealed a transient characteristic of penetrating the alveolar-capillary barrier. The dimensions and size distribution, as well as in vivo aggregation of 99mTc-C60(OH)x, may affect the capability and kinetic process of penetrating the alveolar-capillary barrier. The results provide guidance for further study of the respiratory toxicity of carbon nanomaterials.
Ion irradiation by 500 keV C+ ions has been used to introduce defects into graphene sheets deposited on SiO2 in a controlled way. The combined use of Raman spectroscopy and atomic force microscopy (AFM) allowed one to clarify the mechanisms of disorder formation in single layers, bilayers and multi-layers of graphene. The ratio between the D and G peak intensities in the Raman spectra of single layers is higher than for bilayers and multi-layers, indicating a higher amount of disorder. This cannot be only ascribed to point defects, originating from direct C+–C collisions, but also the different interactions of single layers and few layers with the substrate plays a crucial role. As demonstrated by AFM, for irradiation at fluences higher than 5 × 1013 cm−2, the morphology of single layers becomes fully conformed to that of the SiO2 substrate, i.e. graphene ripples are completely suppressed, while ripples are still present on bilayer and multi-layers. The stronger interaction of a single layer with the substrate roughness leads to the observed larger amount of disorder.
Carbon nanotube (CNT) mediated delivery system of drugs etc. has currently aroused a large interest. Because the delivery system will be ultimately introduced into the human body, the information about the in vivo biological behavior and consequences of CNTs becomes very important. Here, using [14C-taurine]-multi-walled CNTs (MWCNTs) as tracers, we show the biodistribution and translocation pathways of MWCNTs in mice by three different routes. After mice were exposed by intravenous injection, MWCNTs predominately accumulated in liver and retained for long time. Transmission electron micrographs clearly show the remarkable entrapment of MWCNTs in hepatic macrophages (Kupffer cells). The biological index examinations indicate low liver acute toxicity of MWCNTs. Some favorable aspects of MWCNTs being used as a drug nanovehicle are also discussed.
An organic solution-processable functionalized graphene hybrid material with oligothiophene (6THIOP-NH-SPFGraphene) has been synthesized. The thermogravimetry analysis data shows that the hybrid is more stable than its parent graphene oxide as observed with an increased onset temperature. Ultraviolet–visible absorption and fluorescence emission data show that the attachment of the electron-acceptor group (graphene oxide sheet) onto the oligothiophene molecules results in an improved absorption than its parent compound in the whole spectral region and an efficient quenching of photoluminescence. The optical limiting properties were studied by using the open-aperture Z-scan measures at 532 nm, and the results show that 6THIOP-NH-SPFGraphene demonstrated a superior optical limiting effect, better than that of the benchmark optical limiting material C60.
Carbon nanotube (CNT) mediated drug delivery systems have currently aroused a great deal of interest. Such delivery systems for drugs, proteins and genes have been preliminarily studied using cellular and animal models. For the further study of the pharmacokinetics and related biological behaviours of CNTs in vivo, a fast and convenient tracing method is particularly demanded. In this paper, we developed a generally adoptable tracing method for the biodistribution study of functionalized CNTs in vivo. Taurine covalently functionalized multi-walled carbon nanotubes (tau-MWNTs) and Tween-80 wrapped MWNTs (Tween-MWNTs) were labelled with (125)I, and then their distribution in mice was determined. It is interesting that Tween-80 can reduce the RES uptake of MWNTs remarkably. The resulting distribution of (125)I-tau-MWNTs was very consistent with that using (14)C-taurine-MWNTs as the CNTs tracer, which means the easy (125)I labelling method is reliable and effective.
It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via pi-pi stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.
Nanodiamonds (NDs) are receiving increasing attention in materials science and nanotechnology-based industries for a large variety of applications, including protein immobilization, biosensors, therapeutic molecule delivery, and bioimaging. However, limited information is known about their biokinetic behavior and toxicity in vivo. In this article, we investigated the biodistribution of NDs using radiotracer techniques and evaluated its acute toxicity in Kun Ming mice after intratracheal instillation. The biodistribution showed that, besides having the highest retention in the lung, NDs were distributed mainly in the spleen, liver, bone and heart. An analysis of histological morphology and biochemical parameters indicated that NDs could induce dose-dependent toxicity to the lung, liver, kidney and blood. This work provided fundamental data for understanding the biodistribution of NDs and will provide guidance for further study of their toxicity.
(Figure Presented) Repelling bacteria Noncytotoxic Stable in water Mechanically robust TWEEN/reduced graphene oxide composite paper A stable, biocompatible, free-standing "paperlike" material composed of polyoxyethylene sorbitan laurate (TWEEN) and reduced graphene oxide platelets is presented. The TWEEN paper is highly stable in water (no leakage of TWEEN) and sufficiently robust to be handled by hand without breaking (see image). Furthermore, the material is noncytotoxic to three mammalian cell lines and inhibits nonspecific binding of Gram-positive bacteria.
This letter demonstrates that a novel, highly efficient enzyme electrode can be directly obtained using covalent attachment between carboxyl acid groups of graphene oxide sheets and amines of glucose oxidase. The resulting biosensor exhibits a broad linear range up to 28 mM x mm(-2) glucose with a sensitivity of 8.045 mA x cm(-2) x M(-1). The glucose oxidase-immobilized graphene oxide electrode also shows a reproducibility and a good storage stability, suggesting potentials for a wide range of practical applications. The biocompatibility of as-synthesized graphene oxide nanosheets with human cells, especially retinal pigment epithelium (RPE) cells, was investigated for the first time in the present work. Microporous graphene oxide exhibits good biocompatibility and has potential advantages with respect to cell attachment and proliferation, leading to opportunities for using graphene-based biosensors for the clinical diagnosis.
Conjugated-polyelectrolyte (CPE)-functionalized reduced graphene oxide (rGO) sheets are synthesized for the first time by taking advantage of a specially designed CPE, PFVSO(3), with a planar backbone and charged sulfonate and oligo(ethylene glycol) side chains to assist the hydrazine-mediated reduction of graphene oxide (GO) in aqueous solution. The resulting CPE-functionalized rGO (PFVSO(3)-rGO) shows excellent solubility and stability in a variety of polar solvents, including water, ethanol, methanol, dimethyl sulfoxide, and dimethyl formamide. The morphology of PFVSO(3)-rGO is studied by atomic force microscopy, X-ray diffraction, and transmission electron microscopy, which reveal a sandwich-like nanostructure. Within this nanostructure, the backbones of PFVSO(3) stack onto the basal plane of rGO sheets via strong pi-pi interactions, while the charged hydrophilic side chains of PFVSO(3) prevent the rGO sheets from aggregating via electrostatic and steric repulsions, thus leading to the solubility and stability of PFVSO(3)-rGO in polar solvents. Optoelectronic studies show that the presence of PFVSO(3) within rGO induces photoinduced charge transfer and p-doping of rGO. As a result, the electrical conductivity of PFVSO(3)-rGO is not only much better than that of GO, but also than that of the unmodified rGO.
Nanocarbon materials, including single-walled carbon nanotubes (SWCNTs) and graphene, promise various novel biomedical applications (e.g., nanoelectronic biosensing). In this Letter, we study the ability of SWCNT networks and reduced graphene oxide (rGO) films in interfacing several types of cells, such as neuroendocrine PC12 cells, oligodendroglia cells, and osteoblasts. It was found that rGO is biocompatible with all these cell types, whereas the SWCNT network is inhibitory to the proliferation, viability, and neuritegenesis of PC12 cells, and the proliferation of osteoblasts. These observations could be attributed to the distinct nanotopographic features of these two kinds of nanocarbon substrates.
Monocrystalline ZnO nanorods (NRs) with high donor concentration are electrochemically deposited on highly conductive reduced graphene oxide (rGO) films on quartz. The film thickness, optical transmittance, sheet resistance, and roughness of rGO films are systematically studied. The obtained ZnO NRs on rGO films are characterized by X-ray diffraction, transmission electron microscopy, photoluminescence, and Raman spectra. As a proof-of-concept application, the obtained ZnO NRs on rGO are used to fabricate inorganic-organic hybrid solar cells with layered structure of quartz/rGO/ZnO NR/poly(3-hexylthiophene)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (P3HT/PEDOT:PSS)/Au. The observed power conversion efficiency (PCE, eta), approximately 0.31%, is higher than that reported in previous solar cells by using graphene films as electrodes. These results clearly demonstrate that rGO films with a higher conductivity have a smaller work function and show a better performance in the fabricated solar cells.
A simple synthetic route for the preparation of functional nanoscale graphene oxide (NGO), a novel nanocarrier for the loading and targeted delivery of anticancer drugs, is reported. The NGO is functionalized with sulfonic acid groups, which render it stable in physiological solution, followed by covalent binding of folic acid (FA) molecules to the NGO, thus allowing it to specifically target MCF-7 cells, human breast cancer cells with FA receptors. Furthermore, controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin (CPT), onto the FA-conjugated NGO (FA-NGO) via pi-pi stacking and hydrophobic interactions is investigated. It is demonstrated that FA-NGO loaded with the two anticancer drugs shows specific targeting to MCF-7 cells, and remarkably high cytotoxicity compared to NGO loaded with either DOX or CPT only. Considering that the combined use of two or more drugs, a widely adopted clinical practice, often displays much better therapeutic efficacy than that of a single drug, the controlled loading and targeted delivery of mixed anticancer drugs using these graphene-based nanocarriers may find widespread application in biomedicine.
Here we report a graphene oxide amplified electrogenerated chemiluminescence (ECL) of quantum dots (QDs) platform and its efficient selective sensing for antioxidants. Graphene oxide facilitated the CdTe QDs*+ production and triggered O2*- generation. Then, a high yield of CdTe QDs* was formed due to the combination of CdTe QDs*+ and O2*-, leading to an approximately 5-fold ECL amplification. Glutathione is the most abundant cellular thiol-containing peptide, but its selective sensing is an intractable issue in analytical and biochemical communities because its detection is interfered with by some thiol-containing compounds. This platform showed a detection limit of 8.3 microM (S/N = 3) for glutathione and a selective detection linear dependence from 24 to 214 microM in the presence of 120 muM cysteine and glutathione disulfide. This platform was also successfully used for real sample (eye drug containing glutathione) detection without any pretreatment with a wide linear range from 0.04 to 0.29 microg mL(-1).
The ability to organize nanomaterials, e.g., Au nanoparticles (NPs) and graphene oxide (GO) sheets, into ordered structures with high accuracy and resolution on a substrate is crucially important for fundamental studies and applications. In this letter, we developed a simple and efficient method to generate positively charged 11-amino-1-undecanethiol (AUT) templates on Au substrates, which were successfully used for controlled assembly of negatively charged Au NPs or GO sheets from aqueous solution. The templates were obtained by passivation of the exposed Au area with AUT after 16-mercaptohexadecanoic acid (MHA) patterns were generated by dip-pen nanolithography (DPN) on Au. The electrostatic interaction ensures that the Au NPs and GO sheets only adsorb on the designed AUT areas. Importantly, by using this method, the number of Au NPs adsorbed on patterned areas can be controlled, and a single Au NP array was successfully achieved.
Sensitive platform: The use of graphene oxide (GO) as a platform for the sensitive and selective detection of DNA and proteins is presented. The interaction of GO and dye-labeled single-stranded DNA leads to quenching of the dye fluorescence. Conversely, the presence of a target DNA or protein leads to the binding of the dye-labeled DNA and target, releasing the DNA from GO, thereby restoring the dye fluorescence (see picture).
Single walled carbon nanotubes (SWNTs) continue to demonstrate the potential of nanoscaled materials in a wide range of applications. The ability to modulate the mechanical or electrical properties of a material by varying the SWNT component may result in diverse "application tunable" materials. Similarly, biomaterials used in tissue engineering applications may benefit from these characteristics by varying electrical and mechanical properties to enhance or direct tissue specific regeneration. The interactions between SWNTs and cellular systems need to be optimized to integrate these highly hydrophobic nanoparticles within an aqueous environment while maintaining their unique properties. We assessed solubility, conductance, and cellular interactions between four different SWNT preparations (unrefined, refined, and SWNT with either albumin or human plasma adsorbed). Initial interactions between cells and SWNTs were assessed within a 3D environment using a red blood cell lysis model, with longer-term interactions assessing the effects on PC12 and 3T3 fibroblast function when cultured on SWNT-collagen composite hydrogels. After SWNT purification, the lytic effect on red blood cells (RBCs) is significantly reduced from 11% to 0.7%, indicating manufacturing contaminants play a significant role in undesirable cell interactions. Nanotubes with either human plasma or albumin physisorbed onto the nanotube surface were significantly more hydrophilic than either unrefined or refined preparations and displayed improved RBC interactions. Despite improved dispersion, purification, and adsorption of either plasma or albumin, SWNTs caused a significant reduction in conductance. Although the molecular interactions occurring at the cell membrane remain unclear, these investigations have identified two main factors contributing to membrane failure: manufacturing impurities and to a lesser extend the material's innate hydrophobicity. Although purification is a critical step to remove toxic manufacturing contaminants, care must be taken to ensure improved aqueous dispersion does not compromise desirable mechanical and electrical attributes.
A variety of flavonoids, lignans, an alkaloid, a bisbenzyl, coumarins and terpenes isolated from Chinese herbs was tested for antioxidant activity as reflected in the ability to inhibit lipid peroxidation in rat brain and kidney homogenates and rat erythrocyte hemolysis. The pro-oxidant activities of the aforementioned compounds were assessed by their effects on bleomycin-induced DNA damage. The flavonoids baicalin and luteolin-7-glucuronide-6'-methyl ester, the lignan 4'-demethyldeoxypodophyllotoxin, the alkaloid tetrahydropalmatine, the bisbenzyl erianin and the coumarin xanthotoxol exhibited potent antioxidative activity in both lipid peroxidation and hemolysis assays. The flavonoid rutin and the terpene tanshinone I manifested potent antioxidative activity in the lipid peroxidation assay but no inhibitory activity in the hemolysis assay. The lignan deoxypodophyllotoxin, the flavonoid naringin and the coumarins columbianetin, bergapten and angelicin slightly inhibited lipid peroxidation in brain and kidney homogenates. It is worth stressing that the compounds with antioxidant effects in this assay, with the exception of tetrahydropalmatin and tanshinone I, have at least one free aromatic hydroxyl group in structure. Obviously, the aromatic hydroxyl group is very important for antioxidative effects of the compounds. None of the compounds tested exerted an obvious pro-oxidant effect.
The biological behavior of fullerene derivatives shows their considerable potential for medical applications. In order to provide a C(60) derivative for biodistriburtion studies, the (99m)Tc-labeling of C(60)(OH)(x) was optimized. Gamma counting and single photon emission computed tomography (SPECT) were used to assess the biodistribution of the (99m)Tc-labeled compound in mice and rabbits. Biodistribution studies in mice and imaging of rabbits indicated that (99m)Tc-C(60)(OH)(x) was widely distributed in all tissues. A significant percentage of total activity was retained for 48 h, particularly in the kidneys, bone, spleen, and liver. All tissues displayed a slow clearance over 48 h, except for bone, which showed slightly increasing localization within 24 h.
We describe monocrystalline graphitic films, which are a few atoms thick but are nonetheless stable under ambient conditions,
metallic, and of remarkably high quality. The films are found to be a two-dimensional semimetal with a tiny overlap between
valence and conductance bands, and they exhibit a strong ambipolar electric field effect such that electrons and holes in
concentrations up to 1013 per square centimeter and with room-temperature mobilities of ∼10,000 square centimeters per volt-second can be induced by
applying gate voltage.
The development of new and efficient drug delivery systems is of fundamental importance to improve the pharmacological profiles of many classes of therapeutic molecules. Many different types of drug delivery systems are currently available. Within the family of nanomaterials, carbon nanotubes (CNT) have emerged as a new alternative and efficient tool for transporting and translocating therapeutic molecules. CNT can be functionalised with bioactive peptides, proteins, nucleic acids and drugs, and used to deliver their cargos to cells and organs. Because functionalised CNT display low toxicity and are not immunogenic, such systems hold great potential in the field of nanobiotechnology and nanomedicine.
Due to their key roles in a number of biological processes, protein-protein interactions are attractive and important targets, typically involving areas greater than 6 nm2. The disruption of such interactions remains a challenging feat but, in recent years, there has been considerable progress in the design of proteomimetics: molecules that mimic the structure and function of extended regions of protein surfaces. In particular, porphyrins, calixarenes, alpha-helical mimetics and small molecules have successfully modulated significant protein-protein interactions, including those involved in cancer and HIV.
Individualized, chemically pristine single-walled carbon nanotubes have been intravenously administered to rabbits and monitored through their characteristic near-infrared fluorescence. Spectra indicated that blood proteins displaced the nanotube coating of synthetic surfactant molecules within seconds. The nanotube concentration in the blood serum decreased exponentially with a half-life of 1.0 ± 0.1 h. No adverse effects from low-level nanotube exposure could be detected from behavior or pathological examination. At 24 h after i.v. administration, significant concentrations of nanotubes were found only in the liver. These results demonstrate that debundled single-walled carbon nanotubes are high-contrast near-infrared fluorophores that can be sensitively and selectively tracked in mammalian tissues using optical methods. In addition, the absence of acute toxicity and promising circulation persistence suggest the potential of carbon nanotubes in future pharmaceutical applications.
• nanoparticle biodistribution
• nanoparticle toxicity
• luminescence spectroscopy
• single-walled carbon nanotubes
Graphene is a rapidly rising star on the horizon of materials science and condensed-matter physics. This strictly two-dimensional material exhibits exceptionally high crystal and electronic quality, and, despite its short history, has already revealed a cornucopia of new physics and potential applications, which are briefly discussed here. Whereas one can be certain of the realness of applications only when commercial products appear, graphene no longer requires any further proof of its importance in terms of fundamental physics. Owing to its unusual electronic spectrum, graphene has led to the emergence of a new paradigm of 'relativistic' condensed-matter physics, where quantum relativistic phenomena, some of which are unobservable in high-energy physics, can now be mimicked and tested in table-top experiments. More generally, graphene represents a conceptually new class of materials that are only one atom thick, and, on this basis, offers new inroads into low-dimensional physics that has never ceased to surprise and continues to provide a fertile ground for applications.
With the application of carbon nanotubes in biomedical and pharmaceutical sciences, its basic biological properties in vivo have become an issue of strong concern. Water-soluble functionalized multiwall carbon nanotubes (MWNTs) were labeled with radioactive (99m)Tc atoms, and then a tracer was used to study the distribution of MWNTs modified with glucosamine in mice. It shows that MWNTs moved easily among the compartments and tissues of the body, behaving like active molecules although their apparent mean molecular weight is tremendously large. In this study, water-soluble MWNTs were labeled with (99m)Tc for the first time, and all results on the distribution of MWNTs in animals provide useful data for their use in the biomedical field.
Carbon nanotubes are promising new materials for molecular delivery in biological systems. The long-term fate of nanotubes intravenously injected into animals in vivo is currently unknown, an issue critical to potential clinical applications of these materials. Here, using the intrinsic Raman spectroscopic signatures of single-walled carbon nanotubes (SWNTs), we measured the blood circulation of intravenously injected SWNTs and detect SWNTs in various organs and tissues of mice ex vivo over a period of three months. Functionalization of SWNTs by branched polyethylene-glycol (PEG) chains was developed, enabling thus far the longest SWNT blood circulation up to 1 day, relatively low uptake in the reticuloendothelial system (RES), and near-complete clearance from the main organs in approximately 2 months. Raman spectroscopy detected SWNT in the intestine, feces, kidney, and bladder of mice, suggesting excretion and clearance of SWNTs from mice via the biliary and renal pathways. No toxic side effect of SWNTs to mice was observed in necropsy, histology, and blood chemistry measurements. These findings pave the way to future biomedical applications of carbon nanotubes.
A study was conducted to observe the stealth character of PEGylated single-walled carbon nanotubes (PEG-SWCNs) under blood circulation and biodistribution. The skeleton carbon-13 enriched SWNTs were covalently functionalized with diamine-terminated PEG oligomers and the resulting PEG-SWNTs were utilized for in vivo experiments with isotope ratio mass spectrometry. The PEG-SWNTs content in the solution was determined by isotope-MS. The concentrations of PEG-SWNTs in blood were measured by isotope-MS measurements. The low hepatic uptake of nanotubes was observed in the biodistribution. The TEM analysis was utilized to observe the finding of isotope-MS. The liver was digested using HCIO4-H2O2. The amount of PEG conjugation to SWNTs was determined by using NMR and thermogravimetric analysis. Phermacokinetic and biodistribution results show the distinct stealth character of PEG-SWNTs, with measured blood-circulation time.
In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice
- Liu