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Nanotoxicity: The Dark Side of Nanoformulations
Abstract
Nanotoxicity has become the topic of great concern in nanoscience and nanotechnology because of the increasing toxic effects of nanomaterials on living organisms. The toxic patterns of chemotherapeutic drugs, nanomedicines, and nanocarrier are closely associated. Long term exposure of nanocarrier composed of several bioactive (protein and peptide drugs) and chemotherapeutic drugs (anticancerous agents) leads to toxicity, selective induction of cytotoxicity in normal cells and organ. Important factors that contribute directly and significantly to the toxicity of nanoparticles (NPs) constitute particle size, shape and surface area. Apart from size and shape, the structure of the NPs also contributes to nanotoxicity. The review focused on the basic perceptions and mechanisms of nanomaterial-based drug delivery and nanotoxicity is introduced along with a detailed classification of drug delivery approaches i.e., carbon nanotubes, Quantum dots, fullernes and NPs and nanotoxicity models, supported by the most contemporary investigation studies with distinctive emphasis on the communicates between nanotoxicity and nanomedicines research, which is emphasized in order to discover future prospects for developing progressive therapeutic methods. In this framework, the present silhouette focused to assemble and present recent advances, outcomes, and interlinks between nanomaterial-based drug delivery and nanotoxicity disciplines in order to provide inclusive supervision for future nanotechnology-based medicinal research. Reactive oxygen stress with subsequent DNA damage is the major reason for nanotoxicity which can be overcome using green nanoscience uses of antioxidants and surface modification. The silhouette is established with future forecasts on the use of nanocarrier for manipulating the behavior living organism.
... NMs enter our lives through food additives, industrial processes, processed foods, packaging materials, cigarettes, cosmetics, medications, paints, and propellants. These substances can threaten human health, causing diseases like Parkinson's, cancer, Alzheimer's, asthma, bronchitis, emphysema, arrhythmia, urticaria, vasculitis, dermatitis, Crohn's disease, podoconiosis, thrombosis, and hypertension [4]. ...
... NMs are ubiquitous in modern life, present in food additives, industrial processes, cosmetics, medications, and more, with the potential to cause a range of health issues from Parkinson's disease to cancer ( Figure 4) [2,4,141]. However, evaluating their safety through conventional methods is challenging due to the rapid proliferation of NPs and the complexity of the data involved. ...
The rapid expansion of nanotechnology has transformed numerous sectors, with nanoproducts now ubiquitous in everyday life, electronics, healthcare, and pharmaceuticals. Despite their widespread adoption, concerns persist regarding potential adverse effects, necessitating vigilant risk management. This systematic literature review advocates for leveraging artificial intelligence (AI) and machine learning (ML) methodologies to enhance simulations and refine safety assessments for nanomaterials (NMs). Through a comprehensive examination of the existing literature, this study seeks to explain the pivotal role of AI in boosting NMs sustainability efforts across six key research themes. It explores their significance in advancing sustainability, hazard identification, and their diverse applications in this field. In addition, it evaluates the past sustainability strategies for NMs while proposing innovative avenues for future exploration. By conducting this comprehensive analysis, the research aims to illuminate the current landscape, identify challenges, and outline potential pathways for integrating AI and ML to promote sustainable practices within nanotechnology. Furthermore, it advocates for extending these technologies to monitor the real-world behaviour of NMs delivery. Through its thorough investigation, this systematic literature review endeavours to address current obstacles and pave the way for the safe and sustainable utilization of nanotechnology, thereby minimizing associated risks.
... Inorganic type NPs are generally based on metal and metal oxides; for instance, aluminum (Al), gold (Au), silver (Ag), copper (Cu), silica (SiO 2 ), zinc (Zn), and zinc oxide (ZnO), titanium dioxide (TiO 2 ), magnetized iron oxides (Fe 3 O 4 ), and cerium oxide (Ce 2 O 3 ), etc. To date, only applications parts of nanomaterials in vegetable crops have been reviewed by many researchers with few phytotoxicity details Asati et al., 2021;Faiz et al., 2021). Therefore we have provided comprehensive novel mechanistic insights into physiological and molecular understanding of nanoparticle-based toxicity in perishable vegetable crops along with its impact on human health. ...
... Besides NPs associated with phytotoxicity, the accumulation of NPs in the plants sometimes poses a serious threat to human wellbeing (Fig. 3), as these could cycle in the environment through different trophic levels of aqueous or terrestrial food chains subsequently transferring to the human body (Yan and Chen, 2019;Asati et al., 2021). The toxicity of NPs on mammalian cells has been demonstrated in many in vitro studies which are enlisted in Table 3. Ag NPs exposure has been found to diminish lung function and generate lung inflammation, accumulation of NPs in the olfactory bulbs and rat brain (Sung et al., 2008;Kim et al., 2008). ...
With the advancement of nanotechnology, the use of nanoparticles (NPs) and nanomaterials (NMs) in agriculture including perishable vegetable crops cultivation has been increased significantly. NPs/NMs positively affect plant growth and development, seed germination, plant stress management, and postharvest handling of fruits and vegetables. However, these NPs sometimes cause toxicity in plants by oxidative stress and excess reactive oxygen species production that affect cellular biomolecules resulting in imbalanced biological and metabolic processes in plants. Therefore, information about the mechanism underlying interactions of NPs with plants is important for the understanding of various physiological and biochemical responses of plants, evaluating phytotoxicity, and developing mitigation strategies for vegetable crops cultivation. To address this, recent morpho-physiological, biochemical and molecular insights of nanotoxicity in the vegetable crops have been discussed in this review. Further, factors affecting the nanotoxicity in vegetables and mitigation strategies for sustainable cultivation have been reviewed. Moreover, the bioaccumulation and biomagnification of NPs and associated phytotoxicity can cause serious effects on human health which has also been summarized. The review also highlights the use of advanced omics approaches and interdisciplinary tools for understanding the nanotoxicity and their possible use for mitigating phytotoxicity.
... Disruptions in this balance are significant contributors to nanotoxicity. Elevated ROS levels can damage cellular by attacking DNA, proteins, and lipids, ultimately resulting in tissue damage and organ failure [3,10,18]. ...
Iron-based magnetic nanoparticles (NPs) have attracted significant attention in biomedical research, particularly for applications such as cancer detection and therapy, targeted drug delivery, magnetic resonance imaging (MRI), and hyperthermia. This study focuses on the synthesis and glutathione (GSH) functionalization of iron boride (FeB) nanoparticles (NPs) for prospective biomedical use. The GSH-functionalized FeB NPs (FeB@GSH) demonstrated ferromagnetic behavior, with a saturation magnetization (Ms) of 45.8 emu/g and low coercivity (Hc = 1000 Oe), indicating desirable magnetic properties for biomedical applications. Transmission electron microscopy (TEM) analysis of the FeB@GSH revealed well-dispersed nanoparticles with diameters smaller than 30 nm. Comprehensive nanotoxicity and biocompatibility assessments were performed using various healthy and cancer cell lines, including 293 T, HeLa, 3T3, MCF7, HCT116, and CFPAC-1. Cytotoxicity assays were conducted on FeB@GSH-treated cells over a dose range of 0–300 µg/mL during 24-h incubations. Results indicated no significant differences in cell viability between treated and untreated control groups, confirming the biocompatibility of FeB@GSH. Further nanotoxicity evaluations were carried out on 3T3, 293 T, and CFPAC-1 cell lines, focusing on oxidative stress markers and cellular metabolism by measuring antioxidant enzyme activity. Additionally, ion release and mineral metabolism were assessed using inductively coupled plasma mass spectrometry (ICP-MS), revealing no notable variations between the treated and control groups. These findings suggest that FeB@GSH NPs exhibit excellent biocompatibility, making them promising candidates for diverse biomedical applications, including medical imaging, drug delivery systems, and therapeutic interventions.
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... It should not be ignored that inhaled nano-based drug delivery system has certain limitations, which requires high parameters such as particle shape, size and charge, so it has certain challenges in design. At the same time, changes in the physicochemical and structural properties of nanocarriers may be responsible for many material interactions, which may lead to toxicological effects [30], i.e. nanotoxicity, such as causing unwanted oxidative stress and cytotoxicity [31]. Efficient targeting of lung fibrotic cells and improving efficacy are key issues that need to be addressed by the new generation of inhaled nanoformulations. ...
It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.
... additives, processed food, cigarette, cosmetics, packaging materials, forest fires, controlled release medications, propellants, paints, etc. These have the potential to produce risk to human health and cause diseases like Parkinson, Alzheimer, asthma, cancer, emphysema, bronchitis, arrhythmia, dermatitis, vasculitis, urticaria, crohn's disease, hypertension, thrombosis, podoconiosis and many more ( Fig. 1) (Ahamed 2014;Asati et al. 2021). Hence, for a safer and healthier future, there is a need to address this issue and do efficient nanotoxicological testing. ...
The use of nanomaterials in medicine depends largely on nanotoxicological evaluation in order to ensure safe application on living organisms. Artificial intelligence (AI) and machine learning (MI) can be used to analyze and interpret large amounts of data in the field of toxicology, such as data from toxicological databases and high-content image-based screening data. Physiologically based pharmacokinetic (PBPK) models and nano-quantitative structure–activity relationship (QSAR) models can be used to predict the behavior and toxic effects of nanomaterials, respectively. PBPK and Nano-QSAR are prominent ML tool for harmful event analysis that is used to understand the mechanisms by which chemical compounds can cause toxic effects, while toxicogenomics is the study of the genetic basis of toxic responses in living organisms. Despite the potential of these methods, there are still many challenges and uncertainties that need to be addressed in the field. In this review, we provide an overview of artificial intelligence (AI) and machine learning (ML) techniques in nanomedicine and nanotoxicology to better understand the potential toxic effects of these materials at the nanoscale.
... It should be mentioned that in this study we did not consider the issues of nanotoxicity of the used NCMs [55][56][57][58], since the aspects of their further application, which we are developing, do not involve the introduction of their powders into the human body or into the environment. Thus, we assumed the development of devices that provide air disinfection (membranes, filter materials) and antimicrobial coatings. ...
The increasing resistance of bacteria and fungi to antibiotics is one of the health threats facing humanity. Of great importance is the development of new antibacterial agents or alternative approaches to reduce bacterial resistance to available antibacterial drugs. Due to the complexity of their properties, carbon nanomaterials (CNMs) may be of interest for a number of biomedical applications. One of the problems in studying the action of CNMs on microorganisms is the lack of universally standardized methods and criteria for assessing antibacterial and antifungal activity. In this work, using a unified methodology, a comparative study of the antimicrobial properties of the CNM systemic kit against common opportunistic microorganisms, namely Escherichia coli and Staphylococcus aureus, was carried out. Multiwalled carbon nanotubes (MWNTs), catalytic filamentous carbon with different orientations of graphene blocks (coaxial–conical and stacked, CFC), ionic carbon (OLC), and ultrafine explosive nanodiamonds (NDs) were used as a system set of CNMs. The highest antimicrobial activity was shown by NDs, both types of CFCs, and carboxylated hydrophilic MWCNTs. The SEM results point out the difference between the mechanisms of action of UDD and CFC nanotubes.
... Hence, recently more research works have focused towards the toxicity of nanoparticles. Presently, no specific standard method is available for assessing the toxicity of nanoparticles, hence it has become a challenging task [13,14]. ...
In the 21st century, nanotechnology, an interdisciplinary research has become an innovative field and made a new revolution in science and technology. Its unique properties has led an extensive research interest among the researchers and utilized in various fields including biomedical applications. Increased use of nanomaterials in health sciences and medicine aroused a global concern on the biological response, effectiveness, and toxicity of these materials. Therefore, it has become imperative in studying the toxicity of nanomaterial (Nanotoxicology) in therapeutic applications. The main aim of nanotoxicological studies is to determine the toxic/hazardous effects of nanomaterials on humans and to the environment. The toxicity of the nanomaterials depends on various physicochemical properties such as size, shape, surface area, surface chemistry, concentration and several others parameters. Nanomaterials have shown higher toxicity particularly in inhalation studies, hence stringent regulations are made for nanotechnology products to ensure the safety of the products. There are few approaches to overcome these toxicities and improve its therapeutic efficacy and safety. Hence development of nanotechnology should occur on par with risk assessment to identify and subsequently avoid possible dangers in the near future. This article highlights on the different nanomaterials, their unique properties and frameworks for assessing the toxicity of nanomaterials.
Environmental factors may play a critical role in the etiology and pathogenesis of Parkinson’s disease (PD). However, the association of PD with specific chemical species remains largely unknown. Here we prepared three kinds of iron oxide nanoparticles and examined their cytotoxicity in a cellular model of PD. We found that the lysosome-targeted nanoparticles showed significant cytotoxicity in SH-SY5Y cells. Inhibition of AMPK could aggravate the neurotoxicity of lysosome-targeted nanoparticles, as well as mitochondrion-targeted nanoparticles. Alteration of mitochondrial membrane potentials was found to be in agreement with the neurotoxicity of iron nanoparticles. These results suggested an important role of AMPK in regulating iron nanoparticles-associated neurotoxicity.
In the current scenario, the utility of peptide as the targeting ligand has been increased for the efficient diagnosis and treatment of tumor cells. Blood vessels of tumor cells show some molecular receptors on the endothelial cell surface which can differentiate these cells from the remaining vasculature of other normal cells and tissues. Thus, these molecular receptors functioned as the revolutionary and striking target for the effective cancer diagnosis and treatment. Integrin (αvβ3) receptors are highly overexpressed onto the tumor neovasculature and tumor cells. Arginine-Glycine-Aspartic (RGD) peptide may be attached to these overexpressed integrin receptors with high affinity. Therefore, RGD-based systems have been developed for the effective delivery of diagnostic agent and anticancer drug for the diagnosis and treatment of cancer cells, respectively. In this review, an overview of peptide based nanoparticle especially RGD based nanoparticle systems in the field of theranostic application is provided.
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Protection of the skin from the ultraviolet radiation is the prime concern of society. An increase in the adverse effects by ultraviolet (UV) radiation on the skin promoted cosmetic formulators to work in the area of UV blockers and their effective means of delivery. Nanostructured lipid carriers (NLCs) is a modern and successful lipid carrier system in the cosmetic world associated with various advantages i.e., stability, effective drug loading capacity etc. NLCs also permits to load 70% of UV blockers which are sufficient to obtain recommended Sun Protection Factor (SPF) which makes them suitable delivery systems for topical application of the UV blockers.
Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most upto-date statistics related to heart disease, stroke, and the factors in the AHA's Life's Simple 7 (Figure1), which include core health behaviors (smoking, physical activity [PA], diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions. Cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally. The Update also presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure (HF), valvular disease, venous disease, and peripheral arterial disease) and the associated outcomes (including quality of care, procedures, and economic costs). Since 2006, the annual versions of the Statistical Update have been cited >20000 times in the literature. In 2015 alone, the various Statistical Updates were cited '4000 times.
With the recent rapid growth of technological comprehension in nanoscience, researchers have aimed to adapt this knowledge to various research fields within engineering and applied science. Dramatic advances in nanomaterials marked a new epoch in biomedical engineering with the expectation that they would have huge contributions to healthcare. However, several questions regarding their safety and toxicity have arisen due to numerous novel properties. Here, recent studies of nanomaterial toxicology will be reviewed from several physiochemical perspectives. A variety of physiochemical properties such as size distribution, electrostatics, surface area, general morphology and aggregation may significantly affect physiological interactions between nanomaterials and target biological areas. Accordingly, it is very important to finely tune these properties in order to safely fulfill a bio-user’s purpose.
Nanoparticles are emerging as a useful tool for a wide variety of biomedical, consumer and instrumental applications that include drug delivery systems, biosensors and environmental sensors. In particular, nanoparticles have been shown to offer greater specificity with enhanced bioavailability and less detrimental side effects as compared to the existing conventional therapies in nanomedicine. Hence, bionanotechnology has been receiving immense attention in recent years. However, despite the extensive use of nanoparticles today, there is still a limited understanding of nanoparticle-mediated toxicity. Both in vivo and in vitro studies have shown that nanoparticles are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS) levels and/or the levels of pro-inflammatory mediators. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles. Nanoparticles are also known to up-regulate the transcription of various pro-inflammatory genes, including tumor necrosis factor-alpha and IL (interleukins)-1, IL-6 and IL-8, by activating nuclear factor-kappa B (NF-kappa B) signaling. These sequential molecular and cellular events are known to cause oxidative stress, followed by severe cellular genotoxicity and then programmed cell death. However, the exact molecular mechanisms underlying nanotoxicity are not fully understood. This lack of knowledge is a significant impediment in the use of nanoparticles in vivo. In this review, we will provide an assessment of signaling pathways that are involved in the nanoparticle-induced oxidative stress and propose possible strategies to circumvent nanotoxicity.
The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.
This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about the implications for embryo-fetal development and health later in life. Clearly, the potential for hazard remains to be characterized. Considering the increased production and application of nanomaterials and related consumer products a testing strategy for NP should be established. Due to large gaps in data, significant amounts of groundwork are warranted for a testing strategy to be established on a sound scientific basis.
Copyright © 2015. Published by Elsevier Inc.
Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in many fields (paint, industry, medicine, additives in food colorants, and nutritional products). Over the past decade research, TiO2 NPs have been focused on the potential toxic effects of these useful materials. In the present study, we investigated the effects of subacute exposure to TiO2 NPs on emotional behavior in adult Wistar rats, the biochemical parameters, and the histology of organs. Animals were injected intraperitoneally (ip) with TiO2 NPs (20 mg/kg body weight) every 2 days for 20 days. The elevated plus-maze test showed that subacute TiO2 NPs treatment increased significantly the anxious index (AI) compared to control group. The toxicological parameters were assessed 24 h and 14 days after the last injection of TiO2 NPs. Subacute exposure to nanoparticles increased the AST/ALT enzyme ratio and LDH activity. However, the blood cell count remained unchanged, except the platelet count increase. Histological examination showed a little inflammation overall. Moreover, our results provide strong evidence that the TiO2 NPs can induce the liver pathological changes of rats. The intraperitoneal injection of TiO2 NPs increased the accumulation of titanium in the liver, lung, and the brain. The results suggest that TiO2 NPs could alter the neurobehavioral performance of adult Wistar rats and promotes alterations in hepatic tissues.
Iron oxide nanoparticles (INPs) have potential biological, biomedical and environmental applications. These applications require surface modification of the iron oxide nanoparticles, which makes it non-toxic, biocompatible, stable and non-agglomerative in natural and biological surroundings. In the present study, iron oxide nanoparticles (INPs) and chitosan oligosaccharide coated iron oxide nanoparticles (CSO-INPs) were synthesized to evaluate the effect of surface coating on the stability and toxicity of nanoparticles. Comparative in vitro cytotoxicity of nanoparticles was evaluated in HeLa, (Human cervix carcinoma), A549 cells (Human lung carcinoma) and Hek 293 (Human embryonic kidney) cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay along with flow cytometry study for cell viability, membrane integrity, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Morphological alteration in nanoparticles treated cells were analyzed by Acridine orange/Ethidium bromide double staining and electron microscopy. Synthesised nanoparticles were found to be spherical in shape, well dispersed and stable at various pH values, making them suitable for biomedical and environmental applications. Present study also indicates that the chitosan oligosaccharide coating on iron oxide nanoparticles results into the decrease in cellular damage and moderate ROS production, thereby, significantly decreasing the cytotoxic impact of bare iron oxide nanoparticles.
Cancer is the most fatal and lethal disease for our society and the patients suffering from this are increasing continuously. There are many reasons of increasing number of cancer patients. Among others, the modernization of our society is contributing a lot towards cancer genesis. Therefore, the present article high lights the role of modernization for increasing number of cancer patients. Attempts have been made to describe various factors (modernizations) responsible for producing different types of cancers in human beings. Besides, efforts were also made to suggest the preventive and curable measures to control this lethal ailment. Among various suggestions, mass awareness is the most important tool to get rid of this curse serious disease.
This study aimed to observe the effect of intracerebrally injected nano-MnO2 on neurobehavior and the functions of dopaminergic neurons and astrocytes. Nano-MnO2, 6-OHDA, and saline (control) were injected in the substantia nigra and the ventral tegmental area of Sprague-Dawley rat brains. The neurobehavior of rats was evaluated by Morris water maze test. Tyrosine hydroxylase (TH), inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) expressions in rat brain were detected by immunohistochemistry. Results showed that the escape latencies of nano-MnO2 treated rat increased significantly compared with control. The number of TH-positive cells decreased, GFAP- and iNOS-positive cells increased significantly in the lesion side of the rat brains compared with the contralateral area in nano-MnO2 group. The same tendencies were observed in nano-MnO2-injected rat brains compared with control. However, in the the positive control, 6-OHDA group, escape latencies increased, TH-positive cell number decreased significantly compared with nano-MnO2 group. The alteration of spatial learning abilities of rats induced by nano-MnO2 may be associated with dopaminergic neuronal dysfunction and astrocyte activation.
Nanomedicine involves the use of nanoparticles for therapeutic and diagnostic purposes. During the past two decades, a growing number of nanomedicines have received regulatory approval and many more show promise for future clinical translation. In this context, it is important to evaluate the safety of nanoparticles in order to achieve biocompatibility and desired activity. However, it is unwarranted to make generalized statements regarding the safety of nanoparticles, since the field of nanomedicine comprises a multitude of different manufactured nanoparticles made from various materials. Indeed, several nanotherapeutics that are currently approved, such as Doxil and Abraxane, exhibit fewer side effects than their small molecule counterparts, while other nanoparticles (e.g. metallic and carbon-based particles) tend to display toxicity. However, the hazardous nature of certain nanomedicines could be exploited for the ablation of diseased tissue, if selective targeting can be achieved. This review discusses the mechanisms for molecular, cellular, organ, and immune system toxicity, which can be observed with a subset of nanoparticles. Strategies for improving the safety of nanoparticles by surface modification and pretreatment with immunomodulators are also discussed. Additionally, important considerations for nanoparticle safety assessment are reviewed. In regards to clinical application, stricter regulations for the approval of nanomedicines might not be required. Rather, safety evaluation assays should be adjusted to be more appropriate for engineered nanoparticles.
Modified magnetic nanoparticles are used as non-viral gene carriers in biological applications. To achieve successful gene delivery, it is critical that nanoparticles effectually assemble with nucleic acids. However, relatively little work has been conducted on the assemble mechanisms between nanoparticles and DNA, and its effects on transfection efficiency. Using biophysical and biochemical characterization, along with Atomic force microscopy (AFM) and Transmission electron microscopy (TEM), we investigate the morphologies, assembling structures and gene delivering abilities of the PEI modified magnetic nanoparticles (MNPs) gene delivery system. In this gene delivery system, MNP/DNA complexes are formed via binding of DNA onto the surface of MNPs. MNPs are favorable to not only increase DNA concentration but also prevent DNA degradation. Magnetofection experiments showed that MNPs has low cytotoxicity and introduces highly stable transfection in mammalian somatic cells. In addition, different binding ratios between MNPs and DNA result in various morphologies of MNP/DNA complexes and have an influence on transfection efficiency. Dose-response profile indicated that transfection efficiency positively correlate with MNP/DNA ratio. Furthermore, intracellular tracking demonstrate that MNPs move though the cell membranes, deliver and release exogenous DNA into the nucleus.
For the last decade, a big deal of attention is being devoted to study inflammatory response upon exposure to multi/single-walled carbon nanotubes (CNTs) and different fullerene derivatives. In particular, carbon nanoparticles are reported to provoke substantial inflammation in alveolar and bronchial epithelial cells, epidermal keratinocytes, cultured monocyte-macrophage cells etc. We suggest a hypothetical model providing the potential mechanistic explanation for immune and inflammatory responses observed upon exposure to carbon nanoparticles. Specifically, we performed a theoretical study to analyze CNT and C60 fullerene interactions with the available x-ray structures of Toll-like receptors (TLR) homo- and heterodimer extracellular domains. The assumption was based on the fact, that similar to the known TLR ligands both CNT and fullerene induce, in cells, secretion of certain inflammatory protein mediators, such as interleukins and chemokines. These proteins are observed within inflammation downstream processes resulted from ligand molecule dependent inhibition or activation of TLRs –induced signal transduction. Our computational studies have shown that the internal hydrophobic pockets of some TLRs might be capable to bind small-sized carbon nanostructures (5,5 armchair SWCNT containing 11 carbon atom layers and C60 fullerene). High binding scores and minor structural alterations induced in TLR ectodomains upon binding C60 and CNT further supported our hypothesis. Additionally, the proposed hypothesis is strengthened by the indirect experimental findings indicating CNTs and fullerene induce an excessive expression of specific cytokines and chemokines (i.e. IL-8 and MCP1).
Abstract Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.
Silver nanoparticles are nanoparticles of silver which are in the range of 1 and 100 nm in size. Silver nanoparticles have unique properties which help in molecular diagnostics, in therapies, as well as in devices that are used in several medical procedures. The major methods used for silver nanoparticle synthesis are the physical and chemical methods. The problem with the chemical and physical methods is that the synthesis is expensive and can also have toxic substances absorbed onto them. To overcome this, the biological method provides a feasible alternative. The major biological systems involved in this are bacteria, fungi, and plant extracts. The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications. In most of the therapeutic applications, it is the antimicrobial property that is being majorly explored, though the anti-inflammatory property has its fair share of applications. Though silver nanoparticles are rampantly used in many medical procedures and devices as well as in various biological fields, they have their drawbacks due to nanotoxicity. This review provides a comprehensive view on the mechanism of action, production, applications in the medical field, and the health and environmental concerns that are allegedly caused due to these nanoparticles. The focus is on effective and efficient synthesis of silver nanoparticles while exploring their various prospective applications besides trying to understand the current scenario in the debates on the toxicity concerns these nanoparticles pose.
Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation.
Despite their potential for a variety of applications, copper nanoparticles induce very strong inflammatory responses and cellular toxicity following aerosolized delivery. Coating metallic nanoparticles with polysaccharides, such as biocompatible and antimicrobial chitosan, has the potential to reduce this toxicity. In this study, copper nanoparticles were coated with chitosan using a newly developed and facile method. The presence of coating was confirmed using x-ray photoelectron spectroscopy, rhodamine tagging of chitosan followed by confocal fluorescence imaging of coated particles and observed increases in particle size and zeta potential. Further physical and chemical characteristics were evaluated using dissolution and x-ray diffraction studies. The chitosan coating was shown to significantly reduce the toxicity of copper nanoparticles after 24 and 52 h and the generation of reactive oxygen species as assayed by DHE oxidation after 24 h in vitro. Conversely, inflammatory response, measured using the number of white blood cells, total protein, and cytokines/chemokines in the bronchoalveolar fluid of mice exposed to chitosan coated versus uncoated copper nanoparticles, was shown to increase, as was the concentration of copper ions. These results suggest that coating metal nanoparticles with mucoadhesive polysaccharides (e.g. chitosan) could increase their potential for use in controlled release of copper ions to cells, but will result in a higher inflammatory response if administered via the lung.
Photocopiers emit nanoparticles with complex chemical composition. Short-term exposures to modest nanoparticle concentrations triggered upper airway inflammation and oxidative stress in healthy human volunteers in a recent study. To further understand the toxicological properties of copier-emitted nanoparticles, we studied in-vitro their ability to induce cytotoxicity, pro-inflammatory cytokine release, DNA damage, and apoptosis in relevant human cell lines.
Three cell types were used: THP-1, primary human nasal- and small airway epithelial cells. Following collection in a large volume photocopy center, nanoparticles were extracted, dispersed and characterized in the cell culture medium. Cells were doped at 30, 100 and 300 mug/mL administered doses for up to 24 hrs. Estimated dose delivered to cells, was ~10% and 22% of the administered dose at 6 and 24 hrs, respectively. Gene expression analysis of key biomarkers was performed using real time quantitative PCR (RT-qPCR) in THP-1 cells at 5 mug nanoparticles/mL for 6-hr exposure for confirmation purposes.
Multiple cytokines, GM-CSF, IL-1beta, IL-6, IL-8, IFNgamma, MCP-1, TNF-alpha and VEGF, were significantly elevated in THP-1 cells in a dose-dependent manner. Gene expression analysis confirmed up-regulation of the TNF-alpha gene in THP-1 cells, consistent with cytokine findings. In both primary epithelial cells, cytokines IL-8, VEGF, EGF, IL-1alpha, TNF-alpha, IL-6 and GM-CSF were significantly elevated. Apoptosis was induced in all cell lines in a dose-dependent manner, consistent with the significant up-regulation of key apoptosis-regulating genes P53 and Casp8 in THP-1 cells. No significant DNA damage was found at any concentration with the comet assay. Up-regulation of key DNA damage and repair genes, Ku70 and Rad51, were also observed in THP-1 cells, albeit not statistically significant. Significant up-regulation of the key gene HO1 for oxidative stress, implicates oxidative stress induced by nanoparticles.
Copier-emitted nanoparticles induced the release of pro-inflammatory cytokines, apoptosis and modest cytotoxicity but no DNA damage in all three-human cell lines. Taken together with gene expression data in THP-1 cells, we conclude that these nanoparticles are directly responsible for inflammation observed in human volunteers. Further toxicological evaluations of these nanoparticles, including across different toner formulations, are warranted.
Background
Single wall carbon nanotubes (SWCNTs) are considered promising nanoparticles for industrial and biomedical applications; however their potential toxicity in several biological systems, including the feto-placental unit, has been demonstrated. Functionalization of SWCNTs with polyethylene glycol chains (PEG-SWCNTs) dramatically reduces their toxicity, and for this reason PEG-SWCNTs are candidates for biomedical applications. However, no data are available on their safety for the developing embryo, in spite of the clinical and social relevance of this topic. The purpose of this study is therefore to investigate the safety of PEG-SWCNTs for their use as biomedical carriers in pregnancy.
Methods
For toxicological studies, amino-functionalized PEG-SWCNT were intravenously injected in CD1 pregnant mice at different doses (range 0.1-30 μg/mouse), in single or multiple administrations. For biodistribution studies, fluorescently labeled PEG-SWCNTs were obtained by acylation of terminal PEG amino groups with near infrared emitting fluorochromes (PEG-SWCNT-750) and injected at the dosage of 10 μg/mouse, at either day 5.5 (when the placenta is still developing) or day 14.5 of gestation (when the maturation of the placenta is complete).
Results
We found no adverse effects both on embryos and dams up to the dose of 10 μg/mouse. At the dose of 30 μg/mouse, occasional teratogenic effects, associated with placental damage, were detected both when administered as a single bolus (1 out of 10 dams; 1 malformed embryo) or as multiple doses (2 out of 10 dams; 5 malformed embryos). The difference in the prevalence of dams with malformed embryos between the 30 μg exposed group and controls approached the statistical significance (p = 0.06). Hepatic damage in dams was seen only in the multiple exposure group (4 out of 10; p = 0.04 when compared with the single exposure group or controls). PEG-SWCNT-750 reached the conceptus when administered early in pregnancy. At later stages, PEG-SWCNT-750 were detected in the placenta and the yolk sac, but not in the embryo.
Conclusions
PEG-SWCNTs may cause occasional teratogenic effects in mice beyond a threshold dose. Such effect might depend on their ability to reach the feto-placenta unit. Although not automatically transferable to humans, these data should be considered if exposing women during pregnancy.
Cerium dioxide nanoparticles (CeO2 NPs) are an engineered nanomaterial (ENM) that possesses unique catalytic, oxidative, and reductive properties. Currently, CeO2 NPs are being used as a fuel catalyst but these properties are also utilized in the development of potential drug treatments for radiation and stroke protection. These uses of CeO2 NPs present a risk for human exposure; however, to date, no studies have investigated the effects of CeO2 NPs on the microcirculation following pulmonary exposure. Previous studies in our laboratory with other nanomaterials have shown impairments in normal microvascular function after pulmonary exposures. Therefore, we predicted that CeO2 NP exposure would cause microvascular dysfunction that is dependent on the tissue bed and dose. Twenty-four-hour post-exposure to CeO2 NPs (0-400 μg), mesenteric, and coronary arterioles was isolated and microvascular function was assessed. Our results provided evidence that pulmonary CeO2 NP exposure impairs endothelium-dependent and endothelium-independent arteriolar dilation in a dose-dependent manner. The CeO2 NP exposure dose which causes a 50 % impairment in arteriolar function (EC50) was calculated and ranged from 15 to 100 μg depending on the chemical agonist and microvascular bed. Microvascular assessments with acetylcholine revealed a 33-75 % reduction in function following exposure. Additionally, there was a greater sensitivity to CeO2 NP exposure in the mesenteric microvasculature due to the 40 % decrease in the calculated EC50 compared to the coronary microvasculature EC50. CeO2 NP exposure increased mean arterial pressure in some groups. Taken together, these observed microvascular changes may likely have detrimental effects on local blood flow regulation and contribute to cardiovascular dysfunction associated with particle exposure.
Silica nanoparticles (SiO2 NPs) have been shown to exert cytotoxic effects in hepato-cytes and to cause liver injury. In the liver, Kupffer cells (KCs), as the resident macrophages, play an important role in the normal physiology and homeostasis of the liver. Nevertheless, few studies have attempted to clarify the role of KCs in hepatic injury induced by SiO2 NPs. In this study, we treated Buffalo rat liver (BRL) cells with the supernatants of SiO2 NP-stimulated KCs to determine KC-mediated hepatotoxicity and its underlying preliminary mechanism. We also examined the response of KCs and liver injury in vivo after the administration of SiO2 NPs. The results showed that KCs stimulated by SiO2 NPs release large amounts of reactive oxygen species, tumor necrosis factor-α and nitric oxide. After BRL cells were cultured with the supernatants of SiO2 NP-stimulated KCs, the viability of BRL cells was reduced, and increases in aspartate aminotransferase and lactate dehydrogenase leakage were observed. Exposure to SiO2 NPs in vivo caused KC hyperplasia, hepatic inflammation, and oxidative stress, which led to changes in the biochemical composition of the liver. These data suggest that SiO2 NPs activate KCs to mediate hepatic injury and that the preliminary mechanism involves the release of bioactive substances from KCs.
The regulation of engineered nanoparticles requires a widely agreed definition of such particles. Nanoparticles are routinely defined as particles with sizes between about 1 and 100 nm that show properties that are not found in bulk samples of the same material. Here we argue that evidence for novel size-dependent properties alone, rather than particle size, should be the primary criterion in any definition of nanoparticles when making decisions about their regulation for environmental, health and safety reasons. We review the size-dependent properties of a variety of inorganic nanoparticles and find that particles larger than about 30 nm do not in general show properties that would require regulatory scrutiny beyond that required for their bulk counterparts.
Statement of significance:
Drug delivery to the targeted site is a major challenge in clinical medicine. The newly constructed pH responsive biodegradable nanogel consisting of bleomycin revealed pH triggered drug release in a sustained manner to the dermal area offering novel approach against skin cancer. The nanogel system is biodegradable in nature possessing high drug entrapment efficiency and offers patient compliance with biocompatible and cytocompatible characteristics. This nanogel system can thus be highly useful for delivery of anticancer drugs to the skin in a controlled and sustained manner.
Penetration enhancers coated biodegradable polymeric nanogels loaded with cytotoxic drugs applied via the topical route, can be a promising strategy for improving the chemotherapeutic efficiency of skin cancers. The major objective of proposed research was to investigate the in vitro and ex vivo chemotherapeutic potential of double walled PLGA-chitosan biodegradable nanogel entrapped with 5-fluororuacil (5-FU) coated with eucalyptus oil, topically applied onto the skin. 5-FU was first entrapped in PLGA core by solvent evaporation technique followed by coating with cationic chitosan for ionic interaction with anionic skin cancer cell membrane. A surface coating of eucalyptus oil (1%) was employed to improve the penetration efficacy of the nanogel into stratum corneum. The surface modified biodegradable double walled nanogel was characterized for particle size, charge and thermal properties followed by pH dependent in vitro analysis. Human keratinocyte (HaCaT) cell line was employed for the bio- and cyto-compatibility testing prior to the hemolysis assay and coagulation assessment. A porcine skin ex vivo screening was performed for assessing the penetration potential of the nanogels. DLS and TEM revealed a particle size of 170 nm for the double walled nanogels. The nanogels also exhibited high thermal stability as analyzed by thermogravimetry (TG) and differential thermal analysis (DTA). The drug entrapment efficacy was about ~ 45%. The drug release showed sustained release pattern noted up to 24 h. The low hemolysis of 3.31% with short prothrombin time (PT) and activated partial thromboplastin time (APTT) of 13.5 and 33 s respectively, revealed high biocompatibility of the nanogels. The cellular uptake and localization was assessed by confocal microscopy. The cytotoxicity (MTT assay) on HaCaT cell line demonstrated high cytocompatibilty of the nanogels. An ex vivo evaluation using porcine skin displayed efficient and steady state flux of 5-FU from the biodegradable nanogles into the skin, while the histology of the porcine skin revealed enhanced penetration potential of eucalyptus oil coated PLGA-chitosan double walled nanogels. Taken together the in vivo and ex vivo results portend promising potential for the utility of the biodegradable nanogels for treating skin cancers.
Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.
Currently, nanotechnology revolutionizing both scientific and industrial community due to their applications in the fields of medicine, environmental protection, energy, and space exploration. Despite of the evident benefits of nanoparticles, there are still open questions about the influence of these nanoparticles on human health and environment. This is one of the critical issues that have to be addressed in the near future, before massive production of nanomaterials. Manufactured nanoparticles, which are finding ever-increasing applications in industry and consumer products fall into the category of emerging contaminants with ecological and toxicological effects on populations, communities and ecosystems. The existing experimental knowledge gave evidence that inhaled nanoparticles are less efficiently separated than larger particles by the macrophage clearance mechanisms and these nanoparticles are known to translocate through the lymphatic, circulatory and nervous systems to many tissues and organs, including the brain. In this review we highlight adverse impacts of
nanoparticles on human and the environment with special emphasis on green nanoscience as a sustainable alternative.
Numerous investigations have shown that both tissue and cell distribution profiles of anticancer drugs can be controlled by their entrapment in submicronic colloidal systems (nanoparticles). The rationale behind this approach is to increase antitumor efficacy, while reducing systemic side-effects. This review provides an update of tumor targeting with conventional or long-circulating nanoparticles. The in vivo fate of these systems, after intravascular or tumoral administration, is discussed, as well as the mechanism involved in tumor regression. Nanoparticles are also of benefit for the selective delivery of oligonucleotides to tumor cells. Moreover, certain types of nanoparticles showed some interesting capacity to reverse MDR resistance, which is a major problem in chemotherapy. The first experiments, aiming to decorate nanoparticles with molecular ligand for 'active' targeting of cancerous cells, are also discussed here. The last part of this review focus on the application of nanoparticles in imaging for cancer diagnosis.
One fundamental mechanism widely described for nanotoxicity involves oxidative damage due to generation of free radicals and other reactive oxygen species. Indeed, the ability of nanoscale materials to facilitate the transfer of electrons, and thereby promote oxidative damage or in some instances provide antioxidant protection, may be a fundamental property of these materials. Any assessment of a nanoscale material’s safety must therefore consider the potential for toxicity arising from oxidative damage. Therefore, rapid and predictive methods are needed to assess oxidative damage elicited by nanoscale materials. The use of electron spin resonance (ESR) to study free radical related bioactivity of nanomaterials has several advantages for free radical determination and identification. Specifically it can directly assess antioxidant quenching or prooxidant generation of relevant free radicals and reactive oxygen species. In this chapter, we have reported some nonclassical behaviors of the electron spin relaxation properties of unpaired electrons in different fullerenes and the investigation of anti/prooxidant activity by various types of nanomaterials using ESR. In addition, we have reviewed the mechanisms of free radical formation photosensitized by different nanomaterials. This chapter also included the use of spin labels, spin traps and ESR oximetry to systematically examine the enzymatic mimetic activities of nanomaterials.
Sustainable societal and economic development relies on novel nanotechnologies that offer maximum efficiency at minimal environmental cost. Yet, it is very challenging to apply green chemistry approaches across the entire life cycle of nanotech products, from design and nanomaterial synthesis to utilization and disposal. Recently, novel, efficient methods based on nonequilibrium reactive plasma chemistries that minimize the process steps and dramatically reduce the use of expensive and hazardous reagents have been applied to low-cost natural and waste sources to produce value-added nanomaterials with a wide range of applications. This review discusses the distinctive effects of nonequilibrium reactive chemistries and how these effects can aid and advance the integration of sustainable chemistry into each stage of nanotech product life. Examples of the use of enabling plasma-based technologies in sustainable production and degradation of nanotech products are discussed-from selection of precursors derived from natural resources and their conversion into functional building units, to methods for green synthesis of useful naturally degradable carbon-based nanomaterials, to device operation and eventual disintegration into naturally degradable yet potentially reusable byproducts.
The aim of present research was to develop piperine loaded chitosan microspheres to evaluate enhanced hepatoprotective activity in paracetamol induced hepatotoxic mice model. Piperine was extracted from Pippali Piper Longum. Solvent evaporation method was employed to fabricate the microspheres. Optical microscopy demonstrated that the formulation was spherical and had smooth texture with no drug crystals or microsphere aggregation. Formulations containing 2 mg piperine were administered orally to the animal model. In paracetamol induced hepatotoxic mice model, SGOT and SGPT level demonstrated no significant elevation in the blood by the microspheres formulation. The histopathology and enzyme level results suggested that microsphere formulation can passively target hepatoprotective drug to the liver.
The rapidly expanding manufacturing, production and use of nanomaterials has raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Currently, efforts are made to increase the knowledge on the characteristics of nanomaterials that can be used to categorise them into hazard groups according to these characteristics. Grouping helps to gather information on nanomaterials in an efficient way with the aim to aid risk assessment. Here, we discuss different ways of grouping nanomaterials for their risk assessment after inhalation. Since the relation between single intrinsic particle characteristics and the severity of pulmonary inflammation is unknown, grouping of nanomaterials by their intrinsic characteristics alone is not sufficient to predict their risk after inhalation. The biokinetics of nanomaterials should be taken into account as that affects the dose present at a target site over time. The parameters determining the kinetic behaviour are not the same as the hazard-determining parameters. Furthermore, characteristics of nanomaterials change in the life-cycle, resulting in human exposure to different forms and doses of these nanomaterials. As information on the biokinetics and in situ characteristics of nanomaterials is essential but often lacking, efforts should be made to include these in testing strategies. Grouping nanomaterials will probably be of the most value to risk assessors when information on intrinsic characteristics, life-cycle, biokinetics and effects are all combined.
Niosomes containing salbutamol sulphate was prepared using Span 60 as the surfactant, by employing different techniques namely, thin film hydration, hand shaking, ether injection, lipid layer hydration and trans membrane pH gradient method. The drug encapsulation efficiency varied from 62 % to 87 %. In vitro drug release studies was carried out and formulation exhibited retarded release for 24 h. Transmembrane pH gradient method was found to be most satisfactory which released 78.4 % of drug in 24 h. This formulation was lyophilized and characterized by infrared spectroscopy. Tissue distribution studies in albino rats and bio- availability studies in rabbits were carried out.
Natural photosynthesis, a solar-to-chemical energy conversion process, occurs through a series of photo-induced electron transfer reactions in nanoscale architectures that contain light-harvesting complexes, protein-metal clusters, and many redox biocatalysts. Artificial photosynthesis in nanobiocatalytic assemblies aims to reconstruct man-made photosensitizers, electron mediators, electron donors, and redox enzymes for solar synthesis of valuable chemicals through visible light-driven cofactor regeneration. The key requirement in the design of biocatalyzed artificial photosynthetic process is an efficient and forward electron transfer between each photosynthetic component. This review describes basic principles in combining redox biocatalysis with photocatalysis, and highlights recent research outcomes in the development of nanobiocatalytic assemblies that can mimic natural photosystems I and II, respectively. Current issues in biocatalyzed artificial photosynthesis and future perspectives will be briefly discussed.
This book aims to introduce the reader to the design, development, and evaluation processes of new Green Chemistry methodologies. A comprehensive introductory text, it takes a broad view of the subject and integrates a wide variety of topics. Topics covered include: alternative feedstocks, environmentally benign synthetic methodologies, designing safer chemical products, new reaction conditions, alternative solvents and catalyst development, and the use of biosynthesis and biomimetic principles. The reader is introduced to the new evaluation process that encompasses the health and environmental impact of a synthetic pathway from choice of starting materials through to target molecule. Throughout the text, comparisons and contrasts with classical methodologies are offered as illustrative examples. This accessible text is aimed at all those involved with the design, manufacture, use and disposal of chemicals and their products - especially synthetic chemicals at the graduate and professional level, process development chemists and environmental scientists. From reviews of the hardback: ‘An excellent introduction into the fast growing field and the fascinating science of green chemistry.... Should be consulted by anyone who wants to know about environmentally benign chemistry and, especially, by scientists who contemplate adopting its principles in their own research or teaching efforts.’ Science
There have been considerable advances in the field of nanotechnology-based biosensors and diagnostics (NBBD) during the last two decades. These include the production of nanomaterials (NMs), employing them for new biosensing and diagnostic applications, their extensive characterization for in vitro and in vivo applications, and toxicity analysis. All these developments have led to tremendous technology push and successful demonstrations of several promising NBBD. However, there has been a significant lag in their commercialization, especially due to the lack of international regulatory guidelines for evaluating the safety of NMs and the growing public concerns about their toxicity. Despite these numerous advances and the recent regulatory approval of several NMs, it still remains to be seen if NBBD are superior to conventional ones (not based on NMs), reliable, reproducible, cost effective, and robust enough to meet the requirements of industries and healthcare. This manuscript provides a critical review of NBBD, the technology push, and the industrial/healthcare requirements.
The broad application of nanotechnology in medicine, biology, and pharmacology is leading to a dramatic increase of the risk of direct contact of nanoproducts, among which gold nanoparticles (AuNP), with the human organism. The present study aimed at evaluating in vivo the genotoxicity of AuNPs with average size of 40nm and 100nm. A single intraperitoneal treatment of adult male and female Swiss mice (strain H) with AuNPs, at a dose of 3.3mg/kg body weight, had no effect on the frequency of micronucleated polychromatic erythrocytes (MN PCEs) in bone marrow. Conversely, the transplacental treatment with AuNP-100nm, but not with AuNP-40nm, applied intraperitoneally at a dose of 3.3mg/kg to pregnant mice on days 10, 12, 14, and 17 of gestation, resulted in a significant increase in the frequency of MN PCEs in both liver and peripheral blood of mouse fetuses. In parallel, the same treatment with AuNP-100nm, but not with AuNP-40nm, produced significant changes in microRNA expression. In particular, out of 1,281 mouse microRNAs analyzed, 28 were dys-regulated more than two-fold and to a statistically significant extent in fetus lung, and 5 were up-regulated in fetal liver. Let-7a and miR-183 were significantly up-regulated in both organs. The data presented herein demonstrate for the first time the transplacental size-dependent clastogenic and epigenetic effects of AuNPs in mouse fetus, thus highlighting new aspects concerning the putative genotoxicity of AuNPs during a vulnerable period of life.
Water-soluble antioxidant (ascorbic acid, vitamin C) were encapsulated together with poly(L-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic-acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have the mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation efficiency of AgNpPGA/ascorbic-acid within PLGA was determined to be greater than 90%. The entire amount of encapsulated ascorbic acid was released in 68 days, and the entire amount of AgNpPGAs was released in 87 days of degradation. The influence of PLGA/AgNpPGA/ascorbic-acid on cell viability, ROS generation in HepG2 cells, as well as antimicrobial activity against seven different pathogens was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGA/ascorbic-acid particles. We measured the kinetics of ROS formation in HepG2 cells by a DCFH-DA assay, and we found that PLGA/AgNpPGA/ascorbic-acid caused significant decrease in DCF fluorescence intensity, which was two-fold lower than that in control cells after a five-hour exposure. This indicates that PLGA/AgNpPGA/ascorbic-acid microspheres either act as scavengers of intracellular ROS and/or reduce their formation. Also, the results of antimicrobial activity of PLGA/AgNpPGA/ascorbic-acid obtained by the broth microdilution method showed superior and extended activity of these particles. The samples were characterized using FTIR spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, zeta potential and particle size analyzer. This paper presents a new approach to the treatment of infection at the same time with a very pronounced antioxidant effect.
Silver nanoparticles (AgNPs) have anti-cancer effect. However, whether and how these particles could inhibit the growth of acute myeloid leukemia (AML) cells is unclear. In the present study, we prepared AgNPs with various sizes and investigated their cytotoxic effect on AML cells. We found that AgNPs could inhibit the viability of AML cells including the isolates from AML patients. AgNPs caused the production of reactive oxygen species (ROS), losses of mitochondrial membrane potential (MMP), DNA damage and apoptosis. Both vitamin C (Vit C) and N-acetyl-l-cysteine (NAC) could completely reverse the generation of ROS upon AgNPs, however only NAC but not Vit C could protect the cells from losses of MMP, DNA damage and apoptosis thoroughly. Similar results were obtained when cells were treated with silver ions alone. As NAC was not only an antioxidant to scavenge ROS but also a silver ion chelator, these data supported the model that both generation of ROS and release of silver ions played critical roles in the AgNPs-induced cytotoxic effect against AML cells. Taken together, this work elucidated the cytotoxic effect of AgNPs on AML cells and their underlying mechanism and might have significant impact on AML treatment.
Nanocomposites, a high performance material exhibit unusual property combinations and unique design possibilities. With an estimated annual growth rate of about 25% and fastest demand to be in engineering plastics and elastomers, their potential is so striking that they are useful in several areas ranging from packaging to biomedical applications. In this unified overview the three types of matrix nanocomposites are presented underlining the need for these materials, their processing methods and some recent results on structure, properties and potential applications, perspectives including need for such materials in future space mission and other interesting applications together with market and safety aspects. Possible uses of natural materials such as clay based minerals, chrysotile and lignocellulosic fibers are highlighted. Being environmentally friendly, applications of nanocomposites offer new technology and business opportunities for several sectors of the aerospace, automotive, electronics and biotechnology industries.
Liposomal drug delivery systems markedly alter the biodistribution of their associated drugs by delaying drug clearance, retarding drug metabolism, decreasing the volume of distribution, and shifting the distribution in favour of diseased tissues with increased capillary permeability. This increases the therapeutic indices of the associated drugs, by increasing the drug concentration in solid tumours and regions of infection, and reducing the drug concentration in normal tissues. Three liposomal formulations have been approved for clinical use.
Gold nanoparticles (AuNPs) have a number of physical properties that make them appealing for medical applications. For example, the attenuation of X-rays by gold nanoparticles has led to their use in computed tomography imaging and as adjuvants for radiotherapy. AuNPs have numerous other applications in imaging, therapy and diagnostic systems. The advanced state of synthetic chemistry of gold nanoparticles offers precise control over physicochemical and optical properties. Furthermore gold cores are inert and are considered to be biocompatible and non-toxic. The surface of gold nanoparticles can easily be modified for a specific application and ligands for targeting, drugs or biocompatible coatings can be introduced. AuNPs can be incorporated into larger structures such as polymeric nanoparticles or liposomes that deliver large payloads for enhanced diagnostic applications, efficiently encapsulate drugs for concurrent therapy or add additional imaging labels. This array of features has led to the afore-mentioned applications in biomedical fields, but more recently in approaches where multifunctional gold nanoparticles are used for multiple methods, such as concurrent diagnosis and therapy, so called theranostics. The following review covers basic principles and recent findings in gold nanoparticle applications for imaging, therapy and diagnostics, with a focus on reports of multifunctional AuNPs.
Since the advent of technologies to produce genetic knockout and transgenic mice, the number of mouse strains suggested to be useful as models for pregnancy-related complications in the human has risen substantially. Some of these share features in common with fetal growth restriction (FGR) and preeclampsia (PE) and could be useful for investigating aetiologies and for testing potential therapeutics to improve outcome in these diseases. However, since placental pathology is a major underlying factor in both FGR and PE, it is important to understand the similarities and differences in structure and function of the placenta between mice and women. The main aim of this review is to directly compare placental exchange physiology between human and mouse. The review will compare human and mouse in both normal and pathological circumstances, to attempt to answer the question of whether placental studies in the mouse can be translated to the human. The review includes descriptions of placental structure between the species, comparisons of nutrient transport, including amino acids, glucose and calcium, and evidence of how these transport systems are altered in both human FGR and mouse models of this disease. Finally, our review will conclude by examining studies in which mouse models of FGR/PE have been treated with drugs of potential therapeutic value in women and consider whether data obtained in mice can be a prelude for clinical trials in human.
Toxicity of nanoparticles depends on many factors including size, shape, chemical composition, surface area, surface charge, and others. In this study, we compared the toxicity of different sized-silver nanoparticles (AgNPs) which are being widely used in consumer products due to its unique antimicrobial activity. When mice were treated with AgNPs 1 mg/kg for 14 days by oral administration, small-sized AgNPs (22 nm, 42 nm, and 71 nm) were distributed to the organs including brain, lung, liver, kidney, and testis while large-sized AgNPs (323 nm) were not detected in those tissues. The levels of TGF-β in serum were also significantly increased in the treated group of small-sized AgNPs but not in large-sized AgNPs. In addition, B cell distribution was increased in small-sized AgNPs but not in large-sized-AgNPs by the phenotype analysis. However, body weight or in the ratio of organ/body weight were not different between the control group and all the AgNPs-treated groups. The repeated-dose toxicity of AgNPs (42 nm) was also investigated in mice by oral administration for 28 days. By the administration of AgNPs (0.25 mg/kg, 0.50 mg/kg, 1.00 mg/kg), adverse impacts on liver and kidney were observed in a high dose-treated group (1.00 mg/kg), when determined by blood chemistry and histipathological analysis. Cytokines including IL-1, IL-6, IL-4, IL-10, IL-12, and TGF-β were also increased in a dose-dependent manner by repeated oral administration. In addition, B cell distribution in lymphocyte and IgE production were increased. Based on these results, it is suggested that repeated oral administration of nano-sized AgNPs may cause organ toxicity and inflammatory responses in mice.