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Anti-Cancer Potential of Chitosan-Starch Selenium Nanocomposite: Targeting Osteoblastoma and Insights of Molecular Docking
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Due to low toxicity and anti-cancer activity, selenium nanoparticles have been studied to treat various cancers. In the present study, curcumin-loaded selenium-chitosan nanocomposites (CUR-Cs-SeNCs) were prepared, and their inhibitory effect on 4T1 cell line and tumor-bearing mice was reported. FTIR, XRD, EDX, AFM, and SEM analysis confirmed the successful preparation of CUR-Cs-SeNCs. The average size, polydispersity index, and zeta potential of CUR-Cs-SeNCs were 167.43 ± 6.52, 0.18 ± 0.05, and 35.62 ± 5.21 mV, respectively. The cumulative released percentage of curcumin from nanocomposites at pH 5.5 was about 1.8 times higher than at pH 7.4. Moreover, CUR-Cs-SeNCs showed a diffusion-controlled release pattern at pH 6.8 and 5.5. The in vitro cytotoxicity study on 4T1 cells revealed that CUR-Cs-SeNCs dramatically reduced cell proliferation rate compared to pure curcumin. Additionally, the in vivo study confirmed that the CUR-Cs-SeNCs were more successful in reducing the tumor volume than net CUR. More importantly, histopathological studies revealed a more substantial inhibitory effect on tumor growth and liver metastasis of CUR-Cs-SeNCs as compared to free curcumin. No significant signs of toxicity were detected in the vital organs of CUR-Cs-SeNCs-receiving animals. Therefore, considering the pH-dependent release, the improved inhibitory effect on turmeric cells, and the outstanding performance in the animal model, the CUR-Cs-SeNCs may be promising in future tumor management.
Background
Cancer incidence rates are rising at an alarming rate in India and are expected to rise by 12% in the next 5 years. Hence, a thorough knowledge of the existing scope of the cancer problem is required to provide an approach for analyzing and regulating the impact of cancer across the country.
Objectives
This study aimed to determine whether the cancer incidence rates of all the states and union territories across the six geographical regions of India are statistically different from each other or not and also to identify the highly cancer-affected states.
Materials and Methods
The data have been obtained from the website www.indiastat.com from 2009 to 2020. The one-way analysis of variance, followed by Tukey’s test and t -test, is used for the statistical evaluation.
Results
The multiple comparison tests revealed that the difference between the cancer incidence rates is significant in all the states and union territories in every region of India. The highly affected states in the six geographical regions of India are Uttar Pradesh (UP), Tamil Nadu, Bihar, Maharashtra, Assam, and Madhya Pradesh. The most highly affected state among them is UP. These states contributed to nearly half of India’s cancer burden in 2020.
Conclusion
This study offers significant information on the current status of cancer incidence rates in India for 12 years. As India is observing an increase in cancer incidence, therefore, additional efforts are required to strengthen cancer prevention and control strategies, particularly in India’s most cancer-affected states.
The review provides an essential insight into the nanotechnology principles for nano-selenium based materials mainly selenium nanoparticles (SeNPs), selenium nanocomposite (SeNC) and how they can be synthesized, utilized in biomedicine. Various methods of synthesis of nano selenium have revealed extensively in this study. Applications in biomedicine as potential pharmacological agents like antimicrobial, anticancer, anti-diabetic, and anti-oxidative activities have been described extensively in this investigation. The study also demonstrates various methods for the determination of toxicity associated nano selenium under in vitro and in vivo conditions using simple, cost-effective, and green technology principles. In vitro toxicity methods include the use of selected cell lines in which cytotoxic effects can be determined. Phytotoxicity screening is another simplest and reliable method of toxicity assessment. Various animal models like rats, mice, and zebrafish have been widely employed to study the nano selenium-induced toxic effect. Further study will be helpful to explicit the nanotechnology principle of nanoscale derived selenium nanomaterials on diverse applications with high biocompatibility and environmentally friendly.
Graphical Abstract
This work aims to investigate the environmentally sustainable technique to synthesize the copper nanoparticles using bougainvillea flower ethanolic extract at ambient temperature. Copper nanoparticles have considerable potential for reducing the environment’s harmful pigments and nitrogen contaminants. The oxidized copper nanoscale catalysts are enclosed inside nanomaterial, which work as a benign and sustainable resource for capping agents. Ultraviolet spectroscopic, transmission electron microscopy (TEM), and X-ray crystallography (XRD) techniques were used to evaluate the produced oxidized copper nanocrystals. The particles produced have been very robust, are cylindrical in form, and have an outer diameter of 12 nm. Furthermore, under normal conditions, copper oxide (CuO) nanomaterials demonstrated strong photocatalytic efficiency in liquid media for the oxidation of Congo red, bromothymol blue, and 4-nitrophenol in an acidic solution acetic anhydride. Moreover, the CuO nanocrystalline enzyme could be readily vortexed or used for five cycles with an exchange rate of even over 90%. The evaporation process caused around 18% of the loss of weight between 25°C and 190°C, while soil organic breakdown caused almost 31% of the loss of weight around 700°C. As a result, the little reduction in enzymatic effectiveness of the recoverable multilayer CuO substrate might be attributed to catalytic degradation throughout spinning and processing.
Background
The rising economic burden of cancer on patients is an important determinant of access to treatment initiation and adherence in India. Several publicly financed health insurance (PFHI) schemes have been launched in India, with treatment for cancer as an explicit inclusion in the health benefit packages (HBPs). Although, financial toxicity is widely acknowledged to be a potential consequence of costly cancer treatment, little is known about its prevalence and determinants among the Indian population. There is a need to determine the optimal strategy for clinicians and cancer care centers to address the issue of high costs of care in order to minimize the financial toxicity, promote access to high value care and reduce health disparities.
Methods
A total of 12,148 cancer patients were recruited at seven purposively selected cancer centres in India, to assess the out-of-pocket expenditure (OOPE) and financial toxicity among cancer patients. Mean OOPE incurred for outpatient treatment and hospitalization, was estimated by cancer site, stage, type of treatment and socio-demographic characteristics. Economic impact of cancer care on household financial risk protection was assessed using standard indicators of catastrophic health expenditures (CHE) and impoverishment, along with the determinants using logistic regression.
Results
Mean direct OOPE per outpatient consultation and per episode of hospitalization was estimated as ₹8,053 (US 492) respectively. Per patient annual direct OOPE incurred on cancer treatment was estimated as ₹331,177 (US$ 4,171). Diagnostics (36.4%) and medicines (45%) are major contributors of OOPE for outpatient treatment and hospitalization, respectively. The overall prevalence of CHE and impoverishment was higher among patients seeking outpatient treatment (80.4% and 67%, respectively) than hospitalization (29.8% and 17.2%, respectively). The odds of incurring CHE was 7.4 times higher among poorer patients [Adjusted Odds Ratio (AOR): 7.414] than richest. Enrolment in PM-JAY (CHE AOR = 0.426, and impoverishment AOR = 0.395) or a state sponsored scheme (CHE AOR = 0.304 and impoverishment AOR = 0.371) resulted in a significant reduction in CHE and impoverishment for an episode of hospitalization. The prevalence of CHE and impoverishment was significantly higher with hospitalization in private hospitals and longer duration of hospital stay (p < 0.001). The extent of CHE and impoverishment due to direct costs incurred on outpatient treatment increased from 83% to 99.7% and, 63.9% to 97.1% after considering both direct and indirect costs borne by the patient and caregivers, respectively. In case of hospitalization, the extent of CHE increased from 23.6% (direct cost) to 59.4% (direct+ indirect costs) and impoverishment increased from 14.1% (direct cost) to 27% due to both direct and indirect cost of cancer treatment.
Conclusion
There is high economic burden on patients and their families due to cancer treatment. The increase in population and cancer services coverage of PFHI schemes, creating prepayment mechanisms like E-RUPI for outpatient diagnostic and staging services, and strengthening public hospitals can potentially reduce the financial burden among cancer patients in India. The disaggregated OOPE estimates could be useful input for future health technology analyses to determine cost-effective treatment strategies.
Nanotechnology, contrary to its name, has massively revolutionized industries around the world. This paper predominantly deals with data regarding the applications of nanotechnology in the modernization of several industries. A comprehensive research strategy is adopted to incorporate the latest data driven from major science platforms. Resultantly, a broad-spectrum overview is presented which comprises the diverse applications of nanotechnology in modern industries. This study reveals that nanotechnology is not limited to research labs or small-scale manufacturing units of nanomedicine, but instead has taken a major share in different industries. Companies around the world are now trying to make their innovations more efficient in terms of structuring, working, and designing outlook and productivity by taking advantage of nanotechnology. From small-scale manufacturing and processing units such as those in agriculture, food, and medicine industries to larger-scale production units such as those operating in industries of automobiles, civil engineering, and environmental management, nanotechnology has manifested the modernization of almost every industrial domain on a global scale. With pronounced cooperation among researchers, industrialists, scientists, technologists, environmentalists, and educationists, the more sustainable development of nano-based industries can be predicted in the future.
The alizarin red S assay is considered the gold standard for quantification of osteoblast mineralization and is thus widely used among scientists. However, there are several restrictions to this method, e.g., moderate sensitivity makes it difficult to uncover slight but significant effects of potentially clinically relevant substances. Therefore, an adaptation of the staining method is appropriate and might be obtained by increasing the mineralization ability of osteoblasts. In this study, cell culture experiments with human (SaOs-2) and murine (MC3T3-E1) osteoblasts were performed under the addition of increasing concentrations of calcium chloride (1, 2.5, 5, and 10 mM) or calcitonin (1, 2.5, 5, and 10 nM). After three or four weeks, the mineralization matrix was stained with alizarin red S and the concentration was quantified photometrically. Only calcium chloride was able to significantly increase mineralization, and therefore enhanced the sensitivity of the alizarin red S staining in a dose-dependent manner in both osteoblastic cell lines as well as independent of the cell culture well surface area. This cost- and time-efficient optimization enables a more sensitive analysis of potentially clinically relevant substances in future bone research.
Despite numerous treatment methods, there is no gold standard for the treatment of peri-implantitis—an infectious peri-implant disease. Here, we examined selenium nanoparticles (SeNPs) at a wide range of concentrations to investigate their cytotoxicity, regulation of osteoblastic differentiation, and assessed the antibacterial effect against Porphyromonas gingivalis. SeNPs (mean size: 70 nm; shape: near-spherical; concentration: 0–2048 ppm) were tested against the MC3T3-E1 osteoblast precursor cell line and P. gingivalis red complex pathogen. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis was used to evaluate the bone morphogenetic protein 2 (BMP-2) signaling pathway. SeNPs at concentrations of 2–16 ppm showed no obvious cytotoxicity and promoted good mineralization and calcification. SeNPs at concentrations 64 ppm and below influenced gene expression promoting osteoblastic differentiation, whereas at high concentrations inhibited the expression of Runt-related transcription factor 2 (Runx2). The growth of P. gingivalis was significantly inhibited at SeNP concentrations of more than 4 ppm. SeNPs at low concentrations promoted osteoblastic differentiation while strongly inhibiting peri-implantitis pathogen growth. This study represents one of the few in vitro assessments of SeNPs against a red complex pathogen and the regulatory effect on osteoblastic differentiation. The findings demonstrate SeNPs could potentially be used for future application on implant coating.
Zoledronic acid (ZOL) has been approved as the only bisphosphonate for the prevention and treatment of metastatic bone diseases with acceptable safety and tolerability. However, systemic or direct injection of ZOL often causes severe side effects, which limits its clinical application. Here, an innovative nano-drug delivery system, ZOL-loaded hyaluronic acid/polyethylene glycol/nano-hydroxyapatite nanoparticles (HA-PEG-nHA-ZOL NPs), has been found to effectively inhibit the proliferation of three types of human osteosarcoma cell lines (143b, HOS, and MG63) at 1–10 μmol/L, while with low cell cytotoxicity on normal cells. The NPs significantly enhanced the apoptosis-related protein expression and tumor cell apoptosis rate. The NPs could also inhibit the proliferation of osteosarcoma cells by blocking the S phase of the cell cycle. In the orthotopic osteosarcoma nude mice model, local injection of the HA-PEG-nHA-ZOL NPs stimulated tumor necrosis, apoptosis, and granulocyte infiltration in the blood vessels. Altogether, the ZOL nano-delivery system possesses great potential for local treatment to prevent local tumor recurrence and can be applied in clinical osteosarcoma therapy.
Protected cultivation in modern agriculture relies extensively on plastic-originated mulch films, nets, packaging, piping, silage, and various applications. Polyolefins synthesized from petrochemical routes are vastly consumed in plasticulture, wherein PP and PE are the dominant commodity plastics. Imposing substantial impacts on our geosphere and humankind, plastics in soil threaten food security, health, and the environment. Mismanaged plastics are not biodegradable under natural conditions and generate problematic emerging pollutants such as nano-micro plastics. Post-consumed petrochemical plastics from agriculture face many challenges in recycling and reusing due to soil contamination in fulfilling the zero waste hierarchy. Hence, biodegradable polymers from renewable sources for agricultural applications are pragmatic as mitigation. Starch is one of the most abundant biodegradable biopolymers from renewable sources; it also contains tunable thermoplastic properties suitable for diverse applications in agriculture. Functional performances of starch such as physicomechanical, barrier, and surface chemistry may be altered for extended agricultural applications. Furthermore, starch can be a multidimensional additive for plasticulture that can function as a filler, a metaphase component in blends/composites, a plasticizer, an efficient carrier for active delivery of biocides, etc. A substantial fraction of food and agricultural wastes and surpluses of starch sources are underutilized, without harnessing useful resources for agriscience. Hence, this review proposes reliable solutions from starch toward timely implementation of sustainable practices, circular economy, waste remediation, and green chemistry for plasticulture in agriscience
Incorporation of nanoparticles in polymeric matrices to develop polymer nanocomposite with an idea to maximize the “nano-effect” derived out of the nanoparticles and to minimize the disadvantages of the polymer is an emerging area of research. Nanoparticles in the form of nanosheets, nanotubes, nanofibrils and quantum dots are incorporated in polymers to fabricate polymer nanocomposites, which possess tunable mechanical, thermal, electrical, magnetic and optical properties. However, to realize a quality composite, it is imperative to ensure that the selected nanoparticles are uniformly distributed within the matrix and have good compatibility with the matrix material. Thus, one should ensure strict control over the selection and operating parameters of the fabrication method of polymer nanocomposites. The paper presents a review of various fabrication techniques employed to obtain nanoparticle-filled polymer nanocomposites. An effort is also made to understand the effect of such nanoparticles on the mechanical and thermal properties of polymer nanocomposites.
Colorectal cancer is a health problem with high mortality rates and prevalence. Thus, innovative treatment approaches need to be developed. Biogenic nanoparticles are nanomaterials that can be synthesised in biological systems and, compared to chemically synthesised nanoparticles, have better bioavailability while being more cost-effective, eco-friendlier, and less toxic. In our previous studies, the probiotic strain Lactobacillus casei ATCC 393 was used to synthesise selenium nanoparticles (SeNps), which were shown to inhibit colon cancer cell growth in vitro and in vivo. Herein, we have further investigated SeNps’ pro-apoptotic activity and their ability to induce immunogenic cell death (ICD) in colon cancer cells. The SeNps’ effect on Caco-2 cells growth was examined along with their potential to induce caspase activation. Moreover, the expression of typical pro-apoptotic and ICD markers were examined in SeNps-treated HT29 and CT26 cells by flow cytometry, Western blot, ELISA and fluorescence microscopy. Elevated caspase-3 activation and surface phosphatyldoserine, that subsided upon co-incubation with a pan-caspase inhibitor, were detected in SeNps-treated cells. Furthermore, nanoparticles induced modulation of the expression of various apoptosis-related proteins. We also report the detection of biomarkers involved in ICD, namely the translocation of calreticulin and ERp57, the release of HMGB1 and ATP, and the secretion of pro-inflammatory cytokines from SeNps-treated cells. Moreover, RAW246.7 macrophages exhibited a higher rate of phagocytosis against treated CT26 when compared to control cells. Taken together, our findings indicate that treatment with SeNps might be an efficient strategy to destroy tumour cells by inducing apoptotic cell death and triggering immune responses.
Background:
osteoblastoma is a bone-forming tumor accounting for about 1% of all primary bone tumors and 3% of benign bone tumors. The gold-standard treatment is surgical excision; nevertheless, minimally invasive radiological techniques such as thermoablation and, more recently, high intensity focused ultrasound are gaining more importance. The aim of the present paper is to analyze surgical indications based on our experience and on the evidences in the literature.
Methods:
all patients affected by osteoblastoma who underwent surgical excision in January 2009 and December 2018 were reviewed; eleven patients were enrolled in the study. The epidemiological aspects, size of the disease and site of onset, symptoms, surgery type, indications, and results are reported for every case.
Results:
all treatments were based on a preoperative diagnosis; pain was constant in all cases. Intralesional surgeries were performed in 9 out of 11 cases; the remaining 2 cases underwent wide resection. No early or late complications occurred after the surgical procedure. The indications for surgery were lesions very close to nerves or joints, unclear diagnosis, risk of fracture, lesion too large for radiofrequency thermoablation, or failure of minimally invasive treatments. At a medium follow-up of 88 months, no local recurrences were verified.
Conclusions:
osteoblastoma is a rare tumor with difficult diagnosis. Identification is based on symptoms, imaging, and histology. When possible, minimally invasive techniques is preferred for treatment but surgery is still considered the gold standard.
Increasing demand for customized implants and tissue scaffolds requires advanced biomaterials and fabricating processes for fabricating three‐dimensional (3D) structures that resemble the complexity of the extracellular matrix (ECM). Lately, biofabrication approaches such as cell‐laden (soft) hydrogel 3D printing (3DP) have been of increasing interest in the development of 3D functional environments similar to natural tissues and organs. Hydrogels that resemble biological ECMs can provide mechanical support and signaling cues to cells to control their behavior. Although the capability of hydrogels to produce artificial ECMs can regulate cellular behavior, one of the major drawbacks of working with hydrogels is their inferior mechanical properties. Therefore, keeping and enhancing the mechanical integrity of fabricated scaffolds has become an essential matter for 3D hydrogel structures. Herein, 3D‐printed hydrogel‐based nanocomposites (NCs) are evaluated systematically in terms of introducing novel techniques for 3DP of hydrogel‐based materials, properties, and biomedical applications.
Reactive oxygen species (ROS), a class of highly bioactive molecules, have been widely studied in various types of cancers. ROS are considered to be normal byproducts of numerous cellular processes. Typically, cancer cells exhibit higher basal levels of ROS compared to normal cells as a result of an imbalance between oxidants and antioxidants. ROS have a dual role in cell metabolism: At low to moderate levels, ROS act as signal transducers to activate cell proliferation, migration, invasion and angiogenesis. In contrast, high levels of ROS cause damage to proteins, nucleic acids, lipids, membranes, and organelles, leading to cell death. Extensive studies have revealed that anticancer therapies that manipulate ROS levels, including immunotherapies, show promising in vitro as well as in vivo results. In this review, we summarize molecular mechanisms and oncogenic functions that modulate ROS levels and are useful for the development of cancer therapeutic strategies. This review also provides insights into the future development of effective agents that regulate the redox system for cancer treatment.
Reactive oxygen species (ROS) regulate various functions of cells, including cell death, viability, and differentiation, and nanoparticles influence ROS depending on their size and shape. Selenium is known to regulate various physiological functions, such as cell differentiations and anti-inflammatory functions, and plays an important role in the regulation of ROS as an antioxidant. This study aims to investigate the effect of selenium nanoparticles (SeNPs) on the differentiation of osteogenic MC3T3-E1 cells. After fabrication of SeNPs with a size of 25.3 ± 2.6 nm, and confirmation of its oxidase-like activity, SeNPs were added to MC3T3-E1 cells with or without H2O2: 5~20 μg/mL SeNPs recovered cells damaged by 200 μM H2O2 via the intracellular ROS downregulating role of SeNPs, revealed by the ROS staining assay. The increase in osteogenic maturation with SeNPs was gradually investigated by expression of osteogenic genes at 3 and 7 days, Alkaline phosphatase activity staining at 14 days, and Alizarin red S staining at 28 days. Therefore, the role of SeNPs in regulating ROS and their therapeutic effects on the differentiation of MC3T3-E1 cells were determined, leading to possible applications for bone treatment.
Purpose
Redox homeostasis plays an important role in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone engineering. Oxidative stress (OS) is believed to induce osteoporosis by changing bone homeostasis. Selenium nanoparticles (SeNPs), an antioxidant with pleiotropic pharmacological activity, prevent bone loss. However, the molecular mechanism underlying the osteogenic activity during hMSC–SeNP interaction is unclear.
Methods
This study assessed the effects of different concentrations (25, 50, 100, and 300 ng/mL) of SeNPs on the cell viability and differentiation ability of human embryonic stem cell-derived hMSCs. In addition, we analyzed OS markers and their effect on mitogen-activated protein kinase (MAPK) and Forkhead box O3 (FOXO3) during osteogenesis.
Results
SeNPs increased the cell viability of hMSCs and induced their differentiation toward an osteogenic over an adipogenic lineage by enhancing osteogenic transcription and mineralization, while inhibiting Nile red staining and adipogenic gene expression. By preventing excessive reactive oxygen species accumulation, SeNPs increased antioxidant levels in hMSCs undergoing osteogenesis compared to untreated cells. In addition, SeNPs significantly upregulated the gene and protein expression of phosphorylated c-Jun N-terminal kinase (JNK) and FOXO3a, with no significant change in the expression levels of extracellular signal-related kinase (ERK) and p38 MAPK.
Conclusion
The results approved that low concentrations of SeNPs might enhance the cell viability and osteogenic potential of hMSCs by moderating OS. Increased JNK and FOXO3a expression shows that SeNPs might enhance osteogenesis via activation of the JNK/FOXO3 pathway. In addition, SeNP co-supplementation might prevent bone loss by enhancing osteogenesis and, thus, can be an effective candidate for treating osteoporosis through cell-based therapy.
Nanotechnology is defined as the branch of science dealing with extremely small-sized particles with a size in the range of 1–100 nm, which are termed nanoparticles. Due to the extremely small size of nanoparticles, they display unique electronic and optical properties, which differentiate them from their bulk form. Thus, due to the unique properties of nanoparticles, they play a crucial role in a variety of fields, including the biomedical, environmental, agricultural, and industrial fields. Selenium belongs to Group 16 of the periodic table with an atomic number of 34 and its nanoparticles have been highlighted as a potential material to alleviate several problems due to the formation of biofilms, production of ROS, low redox activity, etc. These nanoparticles can be synthesized through chemical, physical and biological methods. Since existing reviews mainly concentrated on the individual applications of selenium nanoparticles such as in diagnosis and therapeutics, the present review mainly highlights the potential activity of selenium nanoparticles in the biomedical domain, making them a potential theragnostic agent. Specifically, this review will present detailed information on the bioimaging and therapeutic activity, together with the role of selenium nanoparticles in the current scenario of the ongoing pandemic (SARS-CoV-2). It will also focus on procedures for their synthesis and properties that make them potential candidates for applications in various domains. Finally, we provide a detailed future outlook.
Synthetic polymers, biopolymers, and their nanocomposites are being studied, and some of them are already used in different medical areas. Among the synthetic ones that can be mentioned are polyolefins, fluorinated polymers, polyesters, silicones, and others. Biopolymers such as polysaccharides (chitosan, hyaluronic acid, starch, cellulose, alginates) and proteins (silk, fibroin) have also become widely used and investigated for applications in medicine. Besides synthetic polymers and biopolymers, their nanocomposites, which are hybrids formed by a macromolecular matrix and a nanofiller (mineral or organic), have attracted great attention in the last decades in medicine and in other fields due to their outstanding properties. This review covers studies done recently using the polymers, biopolymers, nanocomposites, polymer micelles, nanomicelles, polymer hydrogels, nanogels, polymersomes, and liposomes used in medicine as drugs or drug carriers for cancer therapy and underlines their responses to internal and external stimuli able to make them more active and efficient. They are able to replace conventional cancer drug carriers, with better results.
Collagenous and non-collagenous proteins (NCPs) in the extracellular matrix, as well as the coupling mechanisms between osteoclasts and osteoblasts, work together to ensure normal bone metabolism. Each protein plays one or more critical roles in bone metabolism, sometimes even contradictory, thus affecting the final mechanical, physical and chemical properties of bone tissue. Anomalies in the amount and structure of one or more of these proteins can cause abnormalities in bone formation and resorption, which consequently leads to malformations and defects, such as osteoporosis (OP). The connections between key proteins involved in matrix formation and resorption are far from being elucidated. In this review, we resume knowledge on the crosstalk between collagen type I and selected NCPs (Transforming Growth Factor-β, Insulin-like Growth Factor-1, Decorin, Osteonectin, Osteopontin, Bone Sialoprotein and Osteocalcin) of bone matrix, focusing on their possible involvement and role in OP. The different elements of this network can be pharmacologically targeted or used for the design/development of innovative regenerative strategies to modulate a feedback loop in bone remodelling.
Background
Osteoblastoma is a rare, benign, osteolytic neoplasm commonly found in the spine in early adulthood. Here, we review the clinical characteristics, radiographic findings, and surgical management of patients with spinal osteoblastoma.
Material/Methods
Thirteen patients with osteoblastoma who underwent surgery at our institute from June 2008 to November 2017 were enrolled in this study. The American Spinal Injury Association (ASIA) impairment scale was used to assess neurological function. All patients were treated with either total excision or intralesional piecemeal excision without postoperative radiotherapy. Clinical efficacy was evaluated by visual analog scale (VAS) scores, the Oswestry Disability Index (ODI) of nerve function, physical and radiographic examinations, bone fusion, and neurologic status.
Results
The follow-up lasted 23–82 months (average, 43.8 months). The average surgical time was 178.1 minutes (range, 100–230 minutes), with an average intraoperative blood loss of 574 mL (range, 230–1100 mL). Postoperatively, VAS scores decreased from 6.2±1.7 to 0.5±0.7 (P<0.001). The preoperative and final ODI scores were 51.1±7.7 and 22.6±4.9, respectively, reflecting a significant decrease (P<0.001). According to the ASIA classification, 3 patients had grade C, 3 patients had grade D, and 7 patients had grade E disease. Three months postoperatively, 1 patient had grade D and 10 patients had grade E disease; ultimately, all cases were grade E disease. Only 1 patient experienced local recurrence and underwent en bloc marginal resection with postoperative radiotherapy. All patients remained neurologically stable without any major complications.
Conclusions
Accurate intraoperative localization with complete resection is the key to preventing recurrence. Aggressive surgical resection can achieve satisfactory clinical and radiographic outcomes.
Nanoparticles (NPs) serve to reduce the toxicity, enhance bioactivity, improve targeting, and provide versatile means to control the release profile of the encapsulated moiety. Among different NPs, inorganic NPs of metals like Ag, Au, Ce, Fe, Se, Ti and Zn possess a significant place owing to their unique bioactivities in nanoforms. Selenium (Se) is an essential trace element. It is incorporated into selenoproteins as selenocysteine (Sec) representing the most important part of the active center of their enzymatic activities. Many selenoproteins have oxidoreductase activity and, thus, regulate the physiological redox balance. Se has a narrow therapeutic window and the toxicity margins are very delicate whereas the nanoparticles of Se (SeNPs) possess remarkably reduced toxicity. SeNPs have been explored in various oxidative stress and inflammation mediated disorders like arthritis , cancer, diabetes and nephropathy with potential therapeutic benefits. SeNPs constitute an attractive carrier platform to ferry various drugs to the site of action. Herein we have discussed the significance of na-nosizing on the pharmacological activity of Se. The role of SeNPs in pharmacological protection against various inflammatory and oxidative stress mediated conditions is presented. However, it is largely unknown how SeNPs may affect the pharmacokinetics and pharmacodynamics of selenoproteins. Most of the available studies were poorly designed without any comparison to the other Se sources. In the future, detailed studies with inclusion of an appropriate source of Se should be carried out with emphasis on understanding the role of selenoproteins in the observed pharmacological activity.
Nanoparticles serve various industrial and domestic purposes which is reflected in their steadily increasing production volume. This economic success comes along with their presence in the environment and the risk of potentially adverse effects in natural systems. Over the last decade, substantial progress regarding the understanding of sources, fate, and effects of nanoparticles has been made. Predictions of environmental concentrations based on modelling approaches could recently be confirmed by measured concentrations in the field. Nonetheless, analytical techniques are, as covered elsewhere, still under development to more efficiently and reliably characterize and quantify nanoparticles, as well as to detect them in complex environmental matrixes. Simultaneously, the effects of nanoparticles on aquatic and terrestrial systems have received increasing attention. While the debate on the relevance of nanoparticle-released metal ions for their toxicity is still ongoing, it is a re-occurring phenomenon that inert nanoparticles are able to interact with biota through physical pathways such as biological surface coating. This among others interferes with the growth and behaviour of exposed organisms. Moreover, co-occurring contaminants interact with nanoparticles. There is multiple evidence suggesting nanoparticles as a sink for organic and inorganic co-contaminants. On the other hand, in the presence of nanoparticles, repeatedly an elevated effect on the test species induced by the co-contaminants has been reported. In this paper, we highlight recent achievements in the field of nano-ecotoxicology in both aquatic and terrestrial systems but also refer to substantial gaps that require further attention in the future.
This paper describes a simple and reproducible solution phase synthesis approach for selenium nanoparticles by reducing selenium tetrachloride in the presence of ascorbic acid. An optimization study with poly (sodium 4-styrenesulfonate) produced stable and spherical narrowly size distributed nanoparticles (46 nm) which are considered highly monodisperse. The presence of selenium nanoparticles was confirmed by UV-visible spectroscopy for surface plasmon resonance (262 nm), elemental dispersive spectroscopy (11 KeV and 12.5 KeV) and size ranges characterized by dynamic light scattering (PDI = 0.04, size range of optimized nanoparticles = 35 nm to 75 nm), and visualized using scanning and transmission electron microscopy.
Cancer in the broader sense refers to more than 277 different types of cancer disease. Scientists have identified different stage of cancers, indicating that several gene mutations are involved in cancer pathogenesis. These gene mutations lead to abnormal cell proliferation. Genetic disorders caused by heritance or inheritance factors have a pivotal role in the increase of cell growth. With the assistance of technological advances in bioinformatics and molecular techniques, additional information has been obtained that can be useful for early diagnosis and proper treatment The effects of drugs on patients with cancer can predict and even manage some aspects of side effects. In recent years, carcinogenesis mechanisms have been detected by molecular genetic studies. The results of these studies led to an improved understanding of the role of genetic disorders in cancer formation. In this study, our aim was to review molecular aspects of cancer.
Plant-mediated synthesis of selenium nanoparticles (Se-NPs) was done by a simple precipitation method using the aqueous extract of Diospyros montana. The leaf extract to be worked as good capping and stabilizing agent with the formation of stable nanoparticles. These Se-NPs were characterized using UV-Visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), Transmission electron microscopy (TEM), DLS, zeta potential and elemental analysis by energy-dispersive X-ray spectroscopy (EDX). FT-IR spectrum confirms the presence of various functional groups in the aqueous leaf extract of Diospyros montana, which may possibly influence the reduction process of nanoparticles. XRD data confirmed the formation of crystalline Se-NPs. TEM and DLS analysis was determined by the size of Se-NPs ranges from 4 to 16 nm. The zeta potential was obtained at -22.3 mV. DPPH and reducing power activity showed the potential antioxidant property of the biosynthesized Se-NPs. These nanoparticles suspension exhibit more significant antimicrobial activity against both micro organisms such as Gram (+) Staphylococcus aureus, Gram (-) Escherichia coli (bacteria) and Aspergillus niger (fungai). The cytotoxicity of Se-NPs was assayed against human breast-cancer cells (MCF-7). The anticancer property was found that Se-NPs are able to inhibit the cell growth by dose-dependent manner.
Green synthesis of selenium nanoparticles (SeNPs) was achieved by a simple biological procedure using the reducing power of fenugreek seed extract. This method is capable of producing SeNPs in a size range of about 50-150 nm, under ambient conditions. The synthesized nanoparticles can be separated easily from the aqueous sols by a high-speed centrifuge. These selenium nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and elemental analysis by X-ray fluorescence spectrometer (XRF). Nanocrystalline SeNPs were obtained without post-annealing treatment. FTIR spectrum confirms the presence of various functional groups in the plant extract, which may possibly influence the reduction process and stabilization of nanoparticles. The cytotoxicity of SeNPs was assayed against human breast-cancer cells (MCF-7). It was found that SeNPs are able to inhibit the cell growth by dose-dependent manner. In addition, combination of SeNPs and doxorubicin shows better anticancer effect than individual treatments.
Traditional fossil fuels used today have innumerable adverse effects on man and environment. Fuel derived microalgae is reported to be quite a healthier and eco-friendly alternative, as it contains lesser sulphur contents. This current review focuses on the application of nanoparticles in conjugation with microalgae for fuel quality production based on their effect on algal biomass and lipid profile. Processing of the microalgae leads to fuel generation of different viability and precision. Cultivation mode used, harvesting technique utilized and extraction procedure followed will determine the fuel quality and cost associated with it. Nanoparticles can complement any nutritional deficiencies pertaining to growing microalgae in wastewater or ponds. They can stimulate rapid absorption of nutrients and lipid accumulation with antibacterial properties. Aluminium nanoparticles have been reported to enhance the growth in Chlorella sp. by 19 % in a span of 4 days. Lower concentrations seem to favour the growth and biomass quality in microalgae. Iron nanoparticles incorporated in nanofibers of polymer are reported to have higher capture of gas molecules as well as an increase in biomass (794 mg/L) in Chlorella fusca. However, the limit of nanoparticles administration varies from species to species. Iron and zinc nanoparticles have been administered in maximum dosages up to 1000 mg/L till date. The current review highlights the possible application of nanomaterials on microalgal growth and their effect on lipid accumulation, which determines the quality of fuel generated by these strains.
Wood with many of its useful components builds and supports the flora, besides having a commercial significance.
Coatings on the wood are used to preserve it from degradation by physical, chemical, and biological
attacks, and this attribute is considered as a barrier property. Latter due to commercialization, the nonpermeability
to volatile substances and gases is also considered as a part of barrier property. Renewable and
biodegradable cellulose derivatives and lignin have been known for their porosity, hydrophilicity, and barrier
property. Hemicellulose and lignin are not preferred much when compared to cellulose for many commercial
applications. However, the onset of nanotechnology has made utilization of these waste or non-treatable byproducts
of lignocellulosic biomass as potential barrier coatings in the food and paper industry. Moreover, the
weakening process of lignocellulosic biomass by microbial enzymes or microbes conjointly with nanoparticles
decreases the barrier property which could be utilized for biofuel applications. Nanomaterial conjugated
hemicellulose has exhibited the lowest oxygen and vapor permeability level of 0.1799 cm3⋅μm/m2⋅d⋅kPa and
2.75 × 10 11 g/m⋅s respectively, whereas lignin seems to have long term moisture control for up to 189%. The
current review highlights the progress in transforming the lignocellulosic biomass derivatives for food, paper,
and biofuel industrial applications.
Nowadays, cancer is one of the most prominent issues related to human health since it causes more than one-tenth of death cases throughout the world. On the other hand, routine therapeutic approaches in cancer suppression such as radiation therapy, chemotherapy, surgery, etc. due to their undesirable therapeutic outputs, including low efficiency in cancer inhibition, non-targeted drug delivery, nonselective distribution, and enormous side effects, have been indicated inefficient potency in cancer therapy or at least its growth inhibition. As a result, the development of novel and practical therapeutic methods such as nanoparticle-based drug delivery systems can be outstandingly beneficial in cancer suppression. Among various nanoparticles used in the delivery of bioactive to the tumor site, chitosan (CS) nanoparticles have received high attention. CS, poly [β-(1–4)-linked-2-amino-2-deoxy-d-glucose], is a natural linear amino polysaccharide derived from chitin which is made of irregularly distributed d-glucosamine and N-acetyl-d-glucosamine units. CS nanoparticles owing to their appropriate aspects, including nanometric size, great drug loading efficacy, ease of manipulation, non-toxicity, excellent availability and biocompatibility, good serum stability, long-term circulation time, suitable pharmacokinetic and pharmacodynamics, non-immunogenicity, and enhanced drug solubility in the human body, have been designated as an efficient candidate for drug delivery systems. They can be involved in both passive (based on the enhanced permeability and retention effect cancer targeting) and active (receptor-mediated or stimuli-responsive cancer targeting) drug delivery systems for potential cancer therapy. This review presents the properties, preparation, modification, and numerous pharmaceutical applications of CS-based drug nanodelivery systems in the diagnosis and therapy of cancer.
Chitosan is a biopolymer that is natural, biodegradable, and relatively low price. Chitosan has been attracting interest as a matrix of nanocomposites due to new properties for various applications. This study presents a comprehensive overview of common and recent advances using chitosan as a nanocomposite matrix. The focus is to present alternative processes to produce embedded or coated nanoparticles, and the shaping techniques that have been employed (3D printing, electrospinning), as well as the nanocomposites emerging applications in medicine, tissue engineering, wastewater treatment, corrosion inhibition, among others. There are several reviews about single chitosan material and derivatives for diverse applications. However, there is not a study that focuses on chitosan as a nanocomposite matrix, explaining the possibility of nanomaterial additions, the interaction of the attached species, and the applications possibility following the techniques to combine chitosan with nanostructures. Finally, future directions are presented for expanding the applications of chitosan nanocomposites.
A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the "vicious" cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.
In this study, a nanocomposite was prepared from chitosan (Cs) and graphene oxide (GO) with different percentages. The results of Fourier-transform infrared spectroscopy, thermal gravity analysis, and X-ray diffraction showed that the presence of GO nanoparticles increased thermal stability and crystallinity of Cs. Tensile test results showed that the presence of 0.3 wt.% GO in Cs film increased the tensile strength and Young's modulus by 296% and 193%, respectively. The results of bioactivity and biodegradation test showed that the presence of GO in Cs film increased the density of the apatite-like layer on the surface and the degradation time.
The logical research on fundamentally adjusted iron oxide nanoparticles has turned out to expanded in biomedicine because of the improved activity and best biocompatibility. In this present work upgraded bio-restorative
and pharmacotherapeutic property of chitosan iron oxide nanocomposite, which was set up by eco-friendly in
situ substance technique. Characterisation of the synthesised nanocomposite by scanning electron microscopy
(SEM), Fourier transform infrared spectroscopy (FTIR), x-ray diffraction,(XRD) and Vibrating test magnetometer
(VSM) studies reveals that highly stable spherical, electron-dense core shelled rough particles of 50-60 nm. Particle morphology of the synthesised nanocomposite utilising scanning electron microscopy (SEM) uncovers
spherical; thick electron centre shelled harsh particles with the size scope of 50-60 nm. FTIR studies show that
the specific interaction of practical gatherings of chitosan with iron oxide nanoparticles. Crystalline phase and
magnetisation impact of the composite resolved from XRD and VSM studies. Anti-bacterial activity of the nanocomposite examined against human bacterial pathogens which suggest that the readied nanocomposite successfully restrained the development of the tried bacterial strains by recording maximum zone of inhibition, least
minimum inhibition concentration (MIC) and biofilm damage against the both tested strains. 100 μg dosages
of nanocomposites recorded 20.0 and 21.0 mm of the zone of inhibition against E. coli and S. aureus respectively.
Biofilm restraint was additionally observed to be high in nanocomposite treatment by recording lower optical
density of ethanol solubilised biofilm of both tested strains. Anticancer activity was examined against the A549
cell line by the assurance of cell feasibility as opposed to oxidative proteins, articulation example of TNF-α,
Bax, PARP qualities and apoptosis. Composite prompted 50% of cytotoxicity at 80 μg/mL unmistakably uncovers
cytotoxicity against A549 cells. Nanocomposite treatment revealed a high decrease of cell feasibility at all the fixation and most extreme impact seen in 100 μg. Nanocomposite treated cells demonstrated striking changes in cell
morphology, the build-up of atomic material related to trademark changes in against oxidative enzymes, quality
articulation design which brought about apoptosis-like necrotic cell death. The present findings would propose
the conceivable usage of chitosan iron oxide nanocomposite as a viable remedial against safe medication pathogens and malignant growth cells.
Selenium is a rare earth nonmetal and an essential micronutrient for animals, and a trace nutrient for humans. It is known to function as a cofactor for reduction of antioxidant enzymes, such as glutathione peroxidase. The selenium nanobiocomposite synthesized using a co-precipitation method with sizes 20–30 nm were confirmed using scanning electron microscopy and they showed maximum absorption between 300 and 400 nm in the ultra-violet spectrum. Fourier transform infrared and H-nuclear magnetic resonance analysis revealed the involvement of various functional groups in the binding of asparaginase to selenium nanoparticles to form the selenium nanobiocomposite. X-ray diffraction analysis confirmed the hexagonal structure of the selenium nanobiocomposite. Methylthiazolyl diphenyl-tetrazolium bromide assay on HT-29, MG-63 and HEPTO cells loaded with the selenium nanobiocomposite revealed a toxicity of 93.62, 94.24 and 87.68%, respectively, for a selenium nanobiocomposite concentration of 1000\,\upmu \hbox {g ml}^{-1}. The selenium nanobiocomposite of l-asparaginase opens a new arena in cancer treatment.
Aims:
Osteoblastoma-like osteosarcoma is a rare variant of osteosarcoma (1% of all osteosarcomas), histologically similar to osteoblastoma. In the current WHO classification osteoblastoma-like osteosarcoma is classified within the group of conventional (high-grade) osteosarcomas. However, several published cases have been actually regarded as low-grade malignant tumors. Since strict morphologic criteria to distinguish between low-grade and high-grade lesions are not available we reviewed our series of osteoblastoma-like osteosarcomas in the attempt to identify clinical and morphologic features predictive of aggressiveness.
Methods and results:
We retrieved 15 cases of osteoblastoma-like osteosarcoma from the files of the Istituto Ortopedico Rizzoli. Patients received various treatments. Five patients developed metastasis, and 5 patients developed local recurrences (all after incomplete surgery). Eleven patients were alive without disease, while 4 patients died of their disease. Statistical analysis revealed a statistically significant (p = 0.048) lower disease-free survival in patients with areas of conventional (high-grade) osteosarcoma.
Conclusions:
With the important limitation of small cohort of patients, the presence of areas of conventional (high-grade) osteosarcoma is the only parameter to predict the aggressiveness of osteoblastoma-like osteosarcoma. This article is protected by copyright. All rights reserved.
We reported an innovative approach to the synthesis of varisized chitosan-selenium (CS-Se) nanocomposites, which for the first time used CS both as a reductant and stabilizer to synthesize CS-Se nanocomposites. By manipulating the temperature, the well-dispersed CS-Se nanocomposites were synthesized via a simple one pot reaction with the size ranging from 83 to 208 nm before being characterized by TEM, DLS, UV-vis, FTIR, XRD and TG analyses. The results showed that SeO32-was reduced to a stable SeNPs colloid at a comparatively high temperature and the amino group and part of hydroxyl group of CS were conjugated to the surface of SeNPs. Besides, DPPH, ABTS+, hydroxyl radical, metal ion chelating and reducing power assays were carried out to investigate the antioxidant activities of CS-Se nanocomposites, which proved to be concentration-dependent, size-dependent and exhibited good antioxidant activity. The results suggested that CS-Se nanocomposites might be considered as a more appropriate selenium-adding form to achieve antioxidative goals in food.
This study focuses on synthesis and characterization of chitosan ascorbate nanoparticles (CANs) from a salified carboxylate form of chitosan with ascorbic acid. Evident changes were observed in crystallinity and structure of CANs from their parent polymer. CANs exhibited improved antioxidative properties against DPPH, ABTS, and FRAP. In vitro effect of CANs on cervical cancer cells (HeLa) and noncancer human fibroblast cells (WI-38) viability showed portentous toxic effects on cancer cells with reduced viability on increasing CANs concentration. However, no significant effect was observed in the fibroblast cells. Further, in silico docking on cervical cancer protein targets also showed efficient binding.
In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.
Biofunctionalized nanofibers with a desired biological function can be used as a tissue engineering scaffold due to their small fiber diameters and porous structure. In the present study, poly(ε-caprolactone)/poly(m-anthranilic acid) (PCL/P3ANA) nanofibers were biofunctionalized with covalent immobilization of Bone morphogenetic protein-2 (BMP-2) through 1-ethyl-3-(dimethyl-aminopropyl) carbodiimide hydrochloride /N-hydroxysuccinimide (EDC/NHS) activation. FTIR analysis of the nanofiber surfaces confirmed the successful immobilization. The amount of immobilized BMP-2 was determined with bicinchoninic acid (BCA) protein assay. The nanofibers before and after BMP-2 immobilization was non-cytotoxic and enhanced the attachment and proliferation of Saos-2 cells. Biofunctionalization of nanofibers with BMP-2 promoted in vitro osteogenic activity. The alkaline phosphatase activity and calcium mineralization of cells after 14 days of in vitro culture was enhanced on nanofibers with immobilized BMP-2.
Fabrication of nano-sized selenium (Se) particles may help to expend the applications of Se. In this study, we focused on the preparation and characterization of Se nanoparticles (Se NPs) modulated with carrageenan (CA). Furthermore, their influence on osteoblast cell growth was investigated in vitro. Spherical Se-NPs, of 100∼200 nm diameter, were prepared simply by adding κ, ι, and λ-CA, which has sulfate groups, hydroxyl groups, and carboxyl groups. CA-modulated Se NPs (CA-Se NPs) were readily suspended in liquid medium with no precipitation over long time periods. In particular, it was found through Alizarin Red S staining that the growth of osteoblast D1 cells treated with λ-CA-Se NPs was improved significantly. These results suggest that Se NPs can be prepared simply, using CA, have good suspension stability in liquid medium, and λ-CA-Se NPs may induce the growth of osteoblast cells.
Decorin is a prototypical small leucine-rich proteoglycan and epitomizes the multifunctional nature of this critical gene family. Soluble decorin engages multiple receptor tyrosine kinases within the target rich environment of the tumor stroma and tumor parenchyma. Upon receptor binding, decorin initiates signaling pathways within endothelial cells downstream of VEGFR2 that ultimately culminate in a Peg3/Beclin 1/LC3-dependent autophagic program. Concomitant with autophagic induction, decorin blunts capillary morphogenesis and endothelial cell migration, thereby significantly compromising tumor angiogenesis. In parallel within the tumor proper, decorin binds multiple RTKs with high affinity, including Met, for a multitude of oncosuppressive functions including growth inhibition, tumor cell mitophagy, and angiostasis. Decorin is also pro-inflammatory by modulating macrophage function and cytokine secretion. Decorin suppresses tumorigenic growth, angiogenesis, and prevents metastatic lesions in a variety of in vitro and in vivo tumor models. Therefore, decorin would be an ideal therapeutic candidate for combatting solid malignancies.
Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, non-cancerous, osteoblast functions (for example, up to 2 times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of the present study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects. This article is protected by copyright. All rights reserved.
Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
Earlier we described a kinetic assay for quantifying skeletal alkaline phosphatase (ALP) isoenzyme activity in serum. The precision of the assay depends on including ALP standards for the skeletal, hepatic, intestinal, and placental isoenzymes. We wondered whether human osteosarcoma cells could provide an efficient alternative to human bone or Pagetic serum as a source of the skeletal ALP standard. ALP activities prepared from five human osteosarcoma cell lines were compared with a bone-derived ALP standard with respect to heat stability and sensitivity to chemical effectors. Two of the cell lines (SaOS-2 and TE-85) contained ALP activities that resembled the bone-derived standard. We selected SaOS-2 cells for additional evaluation (as a potential source of isoenzyme standard), because they contained 40-50 times more ALP activity than did the TE-85 cells. To include the SaOS-2 cell-derived ALP activity in the quantitative isoenzyme assay, we diluted the enzyme in a solution containing heat-inactivated (i.e., ALP-negative) human serum. Surprisingly, this dilution caused a 60-125% increase in maximum enzyme activity. In the quantitative assay of ALP isoenzyme in serum, the SaOS-2 derived ALP was indistinguishable from the serum skeletal ALP standard, with respect to the above criteria and assay variations. Evidently ALP from SaOS-2 cells is suited as a standard for measuring skeletal ALP activity in this assay.
A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
Alkaline phosphatase (ALP) is the most widely recognized biochemical marker for osteoblast activity. Although its precise function is poorly understood, it is believed to play a role in skeletal mineralization. The aim of this study was to develop an assay suitable for measuring the activity of this enzyme in microtiter plate format. Using the well-characterized osteoblast-like cell line Saos-2, this paper describes an optimized biochemical assay suitable for measuring ALP activity in tissue culture samples. We have determined that a p-nitrophenyl phosphate substrate concentration of 9 mM provides highest enzyme activities. We have found that cell concentration, and hence enzyme concentration, affects both the kinetics and precision of the assay. We also tested several methods of enzyme solubilization and found that freeze-thawing the membrane fractions twice at -70 degrees C/37 degrees C or freeze-thawing once with sonication yielded highest enzyme activities. The activity of the enzyme decreased by 10% after 7 days storage. This assay provides a sensitive and reproducible method that is ideally suited for measuring ALP activity in isolated osteoblastic cells, although sample preparation and storage can influence results.