Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix.

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.

Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation.

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1ß, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood-brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

Prospects of microbial-engineering for the production of graphene and its derivatives: Application to design nanosystms for cancer theranostics.

Cancer is known as one of the leading causes of morbidity and fatality, currently faced by our society. The prevalence of cancer related dieses is rapidly increasing around the world. To reduce the mortality rates, early diagnosis and subsequent treatment of cancer in timely manner is quite essential. Advancements have been made to achieve effective theranostics strategies to tackle cancerous dieses, yet very challenging to overcome this issue. Recently, advances made in the field of nanotechnology have shown tremendous potential for cancer theranostics. Different types of nanomaterials have been successfully employed to develop sophisticated diagnosis and therapy techniques. In this context, graphene and its derivatives e.g. graphene oxide (GO) and reduced graphene oxide (RGO) have been investigated as promising candidates to design graphene-based nanosystems for the diagnosis and therapeutic purpose. Further, to synthesize graphene and its derivatives different types of physicochemical methods are being adopted. However, each method has its own advantage and disadvantages. In this reference, among diverse biological methods, microbial technique can be one of the most promising and eco-friendly approach for the preparation of graphene and its derivatives, particularly GO and RGO. In this review, we summarize studies performed on the preparation of graphene and its derivatives following microbial routes meanwhile focus has been made on the preparation method and the possible mechanism involved therein. Thereafter, we have discussed applications of graphene and its derivatives to developed advanced nanosystem that can be imperative for the cancer theranostics. Results of recent studies exploring applications graphene based nanosystem for the preparation of different types of biosensors for early diagnosis; advanced therapeutic approaches by designing drug delivery nanosystems along with multifunctionality (e.g cancer imaging, drug delivery, photodynamic and photo thermal therapy) in cancer theranostics have been discussed. Particularly, emphasis has been given on the preparation techniques of graphene based nanosystems, being employed in designing of biosensing platforms, drug delivery and multifunctional nanosystems. Moreover, issues have been discussed on the preparation of graphene and its derivatives following microbial technique and the implementation of graphene based nanosystems in cancer theranostics.

Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid ß (Aß) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

Graphene oxide accelerates diabetic wound repair by inhibiting apoptosis of Ad-MSCs via Linc00324/miR-7977/STK4 pathway.

Many studies have shown that graphene oxide (GO) promotes proliferation and differentiation of a variety of stem cells. However, its effect on adipose-derived mesenchymal stem cell (Ad-MSCs) apoptosis is still unclear. Apoptosis is a significant factor affecting stem cell-based treatment of diabetic wounds. Therefore, we explored the effect of GO on Ad-MSC apoptosis and diabetic wound healing. In this study, qRT-PCR was used to detect Ad-MSC expression of LncRNAs, miRNAs, and mRNAs under high-glucose environment. RNA immunoprecipitation (RIP), RNA pull-down, and luciferase assays were used to detect interactions of specific lncRNAs, miRNAs, and mRNAs. The effects of GO on Ad-MSC apoptosis were explored by flow cytometry, TUNEL assay, and Western blot. A diabetic wound model was used to explore the function of Linc00324 on Ad-MSC reparative properties in vivo. As a result, GO inhibited high glucose-induced apoptosis in Ad-MSCs, and Linc00324 contributed to the anti-apoptotic effect of GO. RIP and RNA pull-down confirmed that Linc00324 directly interacted with miR-7977, functioning as a miRNA sponge to regulate expression of the miR-7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad-MSCs in wounds and promoted wound healing. Taken together, these findings suggest GO may be a superior auxiliary material for Ad-MSCs to facilitate diabetic wound healing via the Linc00324/miR-7977/STK4 pathway.

Specific Forms of Graphene Quantum Dots Induce Apoptosis and Cell Cycle Arrest in Breast Cancer Cells.

Graphene quantum dots (GQDs), nanomaterials derived from graphene and carbon dots, are highly stable, soluble, and have exceptional optical properties. Further, they have low toxicity and are excellent vehicles for carrying drugs or fluorescein dyes. Specific forms of GQDs can induce apoptosis and could be used to treat cancers. In this study, three forms of GQDs (GQD (nitrogen:carbon = 1:3), ortho-GQD, and meta-GQD) were screened and tested for their potential to inhibit breast cancer cell (MCF-7, BT-474, MDA-MB-231, and T-47D) growth. All three GQDs decreased cell viability after 72 h of treatment and specifically affected breast cancer cell proliferation. An assay for the expression of apoptotic proteins revealed that p21 and p27 were up-regulated (1.41-fold and 4.75-fold) after treatment. In particular, ortho-GQD-treated cells showed G2/M phase arrest. The GQDs specifically induced apoptosis in estrogen receptor-positive breast cancer cell lines. These results indicate that these GQDs induce apoptosis and G2/M cell cycle arrest in specific breast cancer subtypes and could potentially be used for treating breast cancers.

Research on Graphene and Its Derivatives in Oral Disease Treatment.

Oral diseases present a global public health problem that imposes heavy financial burdens on individuals and health-care systems. Most oral health conditions can be treated in their early stage. Even if the early symptoms of oral diseases do not seem to cause significant discomfort, prompt treatment is essential for preventing their progression. Biomaterials with superior properties enable dental therapies with applications in restoration, therapeutic drug/protein delivery, and tissue regeneration. Graphene nanomaterials have many unique mechanical and physiochemical properties and can respond to the complex oral microenvironment, which includes oral microbiota colonization and high masticatory force. Research on graphene nanomaterials in dentistry, especially in caries, periodontitis therapy, and implant coatings, is progressing rapidly. Here, we review the development of graphene and its derivatives for dental disease therapy.

Multimodal Imaging and Phototherapy of Cancer and Bacterial Infection by Graphene and Related Nanocomposites.

The advancements in nanotechnology and nanomedicine are projected to solve many glitches in medicine, especially in the fields of cancer and infectious diseases, which are ranked in the top five most dangerous deadly diseases worldwide by the WHO. There is great concern to eradicate these problems with accurate diagnosis and therapies. Among many developed therapeutic models, near infra-red mediated phototherapy is a non-invasive technique used to invade many persistent tumors and bacterial infections with less inflammation compared with traditional therapeutic models such as radiation therapy, chemotherapy, and surgeries. Herein, we firstly summarize the up-to-date research on graphene phototheranostics for a better understanding of this field of research. We discuss the preparation and functionalization of graphene nanomaterials with various biocompatible components, such as metals, metal oxides, polymers, photosensitizers, and drugs, through covalent and noncovalent approaches. The multifunctional nanographene is used to diagnose the disease with confocal laser scanning microscopy, magnetic resonance imaging computed tomography, positron emission tomography, photoacoustic imaging, Raman, and ToF-SMIS to visualize inside the biological system for imaging-guided therapy are discussed. Further, treatment of disease by photothermal and photodynamic therapies against different cancers and bacterial infections are carefully conferred herein along with challenges and future perspectives.

Combined treatment with silver graphene quantum dot, radiation, and 17-AAG induces anticancer effects in breast cancer cells.

We aimed to investigate the possible anticancer effects of radiation in combination with 17-allylamino-17-demethoxy geldanamycin (17-AAG) and silver graphene quantum dot (SQD) in breast cancer (BC) cells. MCF-7 BC cells treated with, or without, different concentrations of 17-AAG and synthesized SQD and cellular viability detected. The growth inhibitory effects of low concentrations of 17-AAG with minimally toxic concentration of SQD in combination with 2 Gy of X-ray radiation were examined. The apoptosis induction assessed by acridine orange/ethedium bromide staining. Likewise, the levels of lactate, hydrogen peroxide (H2 O2 ), nitric oxide (NO) were evaluated. The relative gene expression levels of Bax and Bcl-2 were detected by real-time polymerase chain reaction and the Bax/Bcl-2 expression ratio was determined. Moreover, the protein expression of epidermal growth factor receptor (EGFR) was assessed by western blot analysis. Treatment with low concentrations of 17-AAG and SQD at a minimally toxic concentration promoted inhibition of BC cell growth and induced apoptosis. In addition, significant reduction in cell viability was seen in triple combination versus all double and single treatments. Indeed 17-AAG and SQD in combined with radiation significantly increased the H2 O2 and NO versus single and double treated cases. In addition, triple combination treatment showed decreased lactate level in compared tomonotherapies. EGFR protein expression levels were found to decreased in all double and triple combined cases versus single treatments. Additionally, in double and triple treatments, Bax/Bcl2 ratio were higher in compared to single treatments. Treatment with low concentrations of 17-AAG and SQD at a minimally toxic concentration tends to induce anticancer effects and increase the radiation effects when applied with 2 Gy of radiation versus radiation monotherapy.

Graphene Oxide Ameliorates the Cognitive Impairment Through Inhibiting PI3K/Akt/mTOR Pathway to Induce Autophagy in AD Mouse Model.

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system characterised by cognitive impairment. Its major pathological feature is the deposition of ß-amyloid (Aß) peptide, which triggers a series of pathological cascades. Autophagy is a main pathway to eliminate abnormal aggregated proteins, and increasing autophagy represents a plausible treatment strategy against relative overproduction of neurotoxic Aß. Graphene oxide (GO) is an emerging carbon-based nanomaterial. As a derivative of graphene with neuroprotective effects, it can effectively increase the clearance of abnormally aggregated protein. In this article, we investigated the protective function of GO in an AD mouse model. GO (30 mg/kg, intraperitoneal) was administered for 2 weeks. The results of the Morris water maze test and the novel object recognition test suggested that GO ameliorated learning and memory impairments in 5xFAD mice. The long-term potentiation and depotentiation from the perforant path to the dentate gyrus in the hippocampus were increased with GO treatment in 5xFAD mice. Furthermore, GO upregulated the expression of synapse-related proteins and increased the cell density in the hippocampus. Our results showed that GO up-regulated LC3II/LC3I and Beclin-1 and decreased p62 protein levels in 5xFAD mice. In addition, GO downregulated the PI3K/Akt/mTOR signalling pathway to induce autophagy. These results have revealed the protective potential of GO in AD.

Graphene-based nanomaterials for breast cancer treatment: promising therapeutic strategies.

Breast cancer is the most common malignancy in women, and its incidence increases annually. Traditional therapies have several side effects, leading to the urgent need to explore new smart drug-delivery systems and find new therapeutic strategies. Graphene-based nanomaterials (GBNs) are potential drug carriers due to their target selectivity, easy functionalization, chemosensitization and high drug-loading capacity. Previous studies have revealed that GBNs play an important role in fighting breast cancer. Here, we have summarized the superior properties of GBNs and modifications to shape GBNs for improved function. Then, we focus on the applications of GBNs in breast cancer treatment, including drug delivery, gene therapy, phototherapy, and magnetothermal therapy (MTT), and as a platform to combine multiple therapies. Their advantages in enhancing therapeutic effects, reducing the toxicity of chemotherapeutic drugs, overcoming multidrug resistance (MDR) and inhibiting tumor metastasis are highlighted. This review aims to help evaluate GBNs as therapeutic strategies and provide additional novel ideas for their application in breast cancer therapy.

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy.

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities-such as surgery, chemotherapy, and radiation therapy-have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.

An 808 nm Light-Sensitized Upconversion Nanoplatform for Multimodal Imaging and Efficient Cancer Therapy.

Photodynamic therapy (PDT) is commonly employed in clinics to treat the cancer, but because of the hypoxic tumor microenvironment prevalent inside tumors, PDT therapeutic efficiency is not adequate hence limiting the effectiveness of PDT. Therefore, we designed a nanocomposite consisting of reduced nanographene oxide (rGO) modified with polyethylene glycol (PEG), manganese dioxide (MnO2), upconversion nanoparticles (UCNPs), and Chlorin e6 (Ce6) to spark oxygen production from H2O2 with the aim of relieving the tumor hypoxic microenvironments. For in vivo tumor PDT and photothermal therapy (PTT), UCNPs-Ce6-labeled rGO-MnO2-PEG nanocomposites were used as a therapeutic agent, augmenting the therapeutic efficiency of PDT via redox progression through the catalytic H2O2 decomposition pathway and further achieving excellent tumor inhibition. It is important to mention that degradation of MnO2 in an acidic cellular microenvironment leads to the creation of a massive volume of Mn2+ which was employed as a contrast mediator for magnetic resonance imaging (MRI). Our research postulates an approach to spark O2 formation through an internal stimulus to augment the efficiency of MRI- and computerized tomography (CT)-imaging-guided PDT and PTT.

Nanomaterials for oncotherapies targeting the hallmarks of cancer.

An increasing amount of evidence has demonstrated the diverse functionalities of nanomaterials in oncotherapies such as drug delivery, imaging, and killing cancer cells. This review aims to offer an authoritative guide for the development of nanomaterial-based oncotherapies and shed light on emerging yet understudied hallmarks of cancer where nanoparticles can help improve cancer control. With this aim, three nanomaterials, i.e. those based on gold, graphene, and liposome, were selected to represent and encompass metal inorganic, nonmetal inorganic, and organic nanomaterials, and four oncotherapies, i.e. phototherapies, immunotherapies, cancer stem cell therapies, and metabolic therapies, were characterized based on the differential hallmarks of cancer that they target. We also view physical plasma as a cocktail of reactive species and carrier of nanomaterials and focus on its roles in targeting the hallmarks of cancer provided with its unique traits and ability to selectively induce epigenetic and genetic modulations in cancer cells that halt tumor initiation and progression. This review provides a clear understanding of how the physico-chemical features of particles at the nanoscale contribute alone or create synergistic effects with current treatment modalities in combating each of the hallmarks of cancer that ultimately leads to desired therapeutic outcomes and shapes the toolbox for cancer control.

Construction of biocompatible bovine serum albumin nanoparticles composed of nano graphene oxide and AIEgen for dual-mode phototherapy bacteriostatic and bacterial tracking.

BACKGROUND: Efficient and highly controllable antibacterial effect, as well as good biocompatibility are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, nano graphene oxide (NGO)-based near-infrared (NIR) photothermal antibacterial materials was schemed to complex with biocompatible bovine serum albumin (BSA) and aggregation-induced emission fluorogen (AIEgen) with daylight-stimulated ROS-producing property for dual-mode phototherapy in the treatment of antibiotic resistance bacteria. RESULTS: Upon co-irradiation of daylight and NIR laser, NGO-BSA-AIE nanoparticles (NPs) showed superiorly antibacterial effect (more than 99%) both against amoxicillin (AMO)-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by comparison with sing-model phototherapy. Meanwhile, the NGO-BSA-AIE NPs displayed prominent stability and excellently controllable biocompatibility. More importantly, under daylight irradiation, the AIEgen not only produced plentiful ROS for killing bacteria, but also presented fluorescence image for tracking bacteria. CONCLUSIONS: Hence, the designed system provided tempting strategy of employing light as impetus for tracking bacterial distribution and photothermal/photodynamic synergistic treatment of antibiotic resistance antibacterial.

Graphene-Based Nanocomposites for Neural Tissue Engineering.

Graphene has made significant contributions to neural tissue engineering due to its electrical conductivity, biocompatibility, mechanical strength, and high surface area. However, it demonstrates a lack of biological and chemical cues. Also, it may cause potential damage to the host body, limiting its achievement of efficient construction of neural tissues. Recently, there has been an increasing number of studies showing that combining graphene with other materials to form nano-composites can provide exceptional platforms for both stimulating neural stem cell adhesion, proliferation, differentiation and neural regeneration. This suggests that graphene nanocomposites are greatly beneficial in neural regenerative medicine. In this mini review, we will discuss the application of graphene nanocomposites in neural tissue engineering and their limitations, through their effect on neural stem cell differentiation and constructs for neural regeneration.

Multifunctional Platforms Based on Graphene Oxide and Natural Products.

Background and objectives: In the last few years, graphene oxide has attracted much attention in biomedical applications due to its unique physico-chemical properties and can be used as a carrier for both hydrophilic and/or hydrophobic biomolecules. The purpose of this paper was to synthesize graphene oxide and to obtain multifunctional platforms based on graphene oxide as a nanocarrier loaded with few biologically active substances with anticancer, antimicrobial or anti-inflammatory properties such as gallic acid, caffeic acid, limonene and nutmeg and cembra pine essential oils. Materials and Methods: Graphene oxide was obtained according to the method developed by Hummers and further loaded with biologically active agents. The obtained platforms were characterized using FTIR, HPLC, TGA, SEM, TEM and Raman spectroscopy. Results: Gallic acid released 80% within 10 days but all the other biologically active agents did not release because their affinity for the graphene oxide support was higher than that of the phosphate buffer solution. SEM characterization showed the formation of nanosheets and a slight increase in the degree of agglomeration of the particles. The ratio I2D/IG for all samples was between 0.18 for GO-cembra pine and 0.27 for GO-limonene, indicating that the GO materials were in the form of multilayers. The individual GO sheets were found to have less than 20 µm, the thickness of GO was estimated to be ~4 nm and an interlayer spacing of about 2.12 Å. Raman spectroscopy indicated that the bioactive substances were adsorbed on the surface and no degradation occurred during loading. Conclusions: These findings encourage this research to further explore, both in vitro and in vivo, the biological activities of bioactive agents for their use in medicine.

Directly probing the dissociation effects of graphene oxide nanosheets on hIAPP fibrils.

The aggregation of human islet amyloid polypeptides (hIAPP) to mature fibrils is considered as the main cause of type II diabetes. Therefore destroying the pre-formed hIAPP fibrils is expected to be a promising strategy for therapeutic treatments. In this work, the dissociation effects of graphene oxide (GO) nanosheets on hIAPP mature fibrils are investigated. The results clearly demonstrate that hIAPP fibrils can be quickly adsorbed on the GO surface and efficiently broken into short fragments. Meanwhile, the ß-sheet structures of hIAPP fibrils are greatly destroyed. Particularly, in situ atomic force microscopy was applied to monitor the real-time interaction between hIAPP fibrils and GO nanosheets. It provides distinct evidence that the disruption of hIAPP fibrils by GO nanosheets mainly occurs at the GO edges. Size-dependent experiments further justify the interfere of edge contribution, which suggest small-sized GO nanosheets exhibit better dissociation ability than large-sized ones. Therefore, this study not only provides valuable information that GO nanosheets (especially small-sized ones) can act as efficient nanoblades to break hIAPP fibrils, but also suggests a powerful and widely available methodology for investigating real-time interaction between nanomaterials and biomolecules.

Optimizing the nanostructure of graphene oxide/silver/arginine for effective wound healing.

In this study, we introduce a novel graphene oxide/silver/arginine (GO/Ag/Arg) nanohybrid structure, which can act as an angiogenesis promoter and provide antibacterial nanostructure for improving the wound healing process. GO/Ag nanostructure has been optimized in terms of the GO/Ag mass ratio and pH values using central composite design and the response surface method to increase the Ag loading efficiency. Then, Arg was chemically introduced to the surface of GO/Ag nanostructure. Electrospun polycaprolactone (PCL)-GO/Ag/Arg nanocomposite was successfully fabricated and characterized. The synthesized nanocomposite demonstrated not only a great antibacterial effect on both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial species, but appropriate biocompatibility against L929 fibroblastic cell lines. The results demonstrated that the preparation of the PCL-GO/Ag/Arg nanocomposite at a concentration of 1.0 wt% GO/Ag/Arg possessed the best biological and mechanical features. In vivo experiments also revealed that the use of optimized PCL-GO/Ag/Arg nanocomposite, after 12 d of treatment, led to significant increase in the healing process and also regeneration of the wound via reconstruction of a thickened epidermis layer on the wound surface, which was confirmed by histological analysis. In conclusion, the proposed approach can introduce a novel notion for preparing antibacterial material that significantly promotes angiogenesis.

Cytotoxicity of Graphene Oxide (GO) and Graphene Oxide Conjugated Losartan Potassium (GO-LP) on Neuroblastoma (NB41A3) Cells.

Despite several advancements in the biomedical sciences, an efficient cancer therapy still remains a challenge. Nanomedicines have shown potential to overcome certain roadblocks faced in the existing treatment modalities. Losartan potassium (LP) which is a known vasodilator also exhibits anti fibrolytic and anti-metastatic properties altogether. Further, also being a potential angiotensin II type 1 receptor antagonist, it has been well explored for down regulating tumourogenic biomarkers like VEGF-A (Vascular endothelial growth factor A) and suppression of neovascularization, making it a suitable drug to target for cancer treatment. Besides this, it too reflected the stimulation of pro apoptotic signaling pathways. But due to its lower bioavailability and extensive hepatic metabolism its therapeutic index reduces down. Thus, the present study is focused on designing a nano-delivery system using graphene oxide (GO) as a nano-vehicle and conjugated the LP with it. Then, the successful synthesis of GO and GO-LP nano conjugates were characterized by high-resolution transmission electron microscopy, X-ray diffraction, FTIR and UV visible spectroscopy, confirming the formation of nanosheets. The qualitative morphological evaluation of NB41A3 neuroblastoma cell line treated with bare GO, LP and GO-LP using microscopy and DAPI staining revealed the inhibitory action of GO-LP nano conjugate on cell proliferation. Additionally, the cytotoxicity was also estimated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), Nitric oxide (NO) and Lactate dehydrogenase (LDH) assays. The results show that GO-LP significantly suppresses the cell viability in comparison to control and bare GO suggesting that the designed system may express its potential to be used with existing chemo drugs for the treatment of neural cancers.