Self-assembled chitosan polymer intercalating peptide functionalized gold nanoparticles as nanoprobe for efficient imaging of urokinase plasminogen activator receptor in cancer diagnostics.

Targeting cell surface receptors for specific drug delivery in cancer has garnered lot of attention. Urokinase plasminogen activator receptor (uPAR), a surface biomarker, is overexpressed on many tumours including breast, colorectal, prostate, and ovarian cancers. Binding of growth factor domain (GFD) of urokinase plasminogen activator (uPA) with uPAR lead to its close conformation, and allow somatomedin B domain (SMB) of vitronectin binding by allosteric modulation. In-silico docking of uPAR with GFD and SMB peptides was performed to identify potential binding affinity. Herein, we report fluorescently labeled peptide functionalized AuNPs with a mixed self-assembled monolayer of intercalating chitosan polymer for efficient targeting and imaging of uPAR-positive cells. The biophysical characterization of nanoconjugates and uPAR-specific targeting was assessed by FACS, cell adhesion, and fluorescence imaging. AuNPs/chitosan/GFD+SMB peptides showed higher uptake as compared to AuNPs/chitosan/GFD, and AuNPs/chitosan/SMB that can be utilized as a tool for molecular targeting and imaging in metastasis.

Water-Templated, Polysaccharide-rich Bioartificial 3D Microarchitectures as Extra-Cellular Matrix Bioautomatons.

This is the first report of exploiting the "quasi-spherical" shape of water molecules for recapitulating a true human extracellular matrix (ECM). Herein, water behaved as a quasi-spherical porogen, for engineering polysaccharide-rich and chemically defined 3D-microarchitecture, with semi-interpenetrating networks (S-IPNs). Furthermore, their viscoelastic behavior along with a heterogeneous, fibroporous morphology, facilitated instructive, self-remodeling of the bioartificial scaffolds, thence effectively permitting and promoting the growth of 3D tumor spheroids of divergent origins. The hybrid composites displayed reproducible, uniform tumor spheroids with a Z-depth of ∼65 ± 2 µm in case of human adenocarcinoma (DLD-1) and ∼54 ± 3 µm for human glioblastoma cells (U-251) (vs. nonuniform spheroids, on Agarose matrix). Thereafter, their capacity for anticancer drug screening was examined using limited cancer drugs. The conflicting drug screening results for Etoposide's reduced efficacy on glioblastoma cells cultured on our 3D matrix could be ascribed to decreased drug access and thus lower ingression. Nonetheless, adenocarcinoma's resistance to Camptothecin was paralleled. Moreover, their potential for real-time, high-content, phenotypic precision oncology was affirmed by the exceptional transparency of the synthesized composite. Since this 3D microarchitecture typifies ECM bioautomaton, this matrix can also be wielded for precision oncology.

Electrochemically synthesized highly crystalline nitrogen doped graphene nanosheets with exceptional biocompatibility.

This work reports first electrochemical preparation of exceptionally biocompatible, highly crystalline, and well exfoliated nitrogen doped graphene nanosheets (eNGS) from carbon nanosheets for the development of mighty platforms in the field of modern biosensing and other biological applications for human welfare. eNGS displayed exceptional biocompatibility. Administration of the as-synthesized eNGS to rat models did not lead to any significant deviation or inimical consequences in its functional observation battery (FOB) tests, GSH levels or the histology of the vital organs of the rat models. The pictomicrographs of myocytes nuclei and myofibrillar for heart, hippocampus (CA1) section for brain, central vein, and hepatocytes for liver and parenchyma, tubules and glomeruli for kidney also remained unaffected. Moreover, the resultant nanoelectrocatalyst displayed enhanced electrochemical performance towards real-time sensing of dopamine (DA) from human urine sample in the presence of interferences, such as ascorbic acid (AA) and uric acid (UA).

Therapeutic Implications of Superoxide Dismutase And Its Importance in Kinase Drug Discovery.

In recent years, several scientific investigations have reported the therapeutic implications of superoxide dismutase (SOD) against oxidative stress and -induced pathology in clinical and preclinical trials. Indeed, various kinase, molecular signaling and physiological process has altered by reactive oxygen species. In spite of the abundant available literature reports, patents, clinical trials and commercialized products, the therapeutic application of SOD as a potential drug still remains unclear. Owing to the technical challenges associated with the utilization of SOD as a drug, we revisited the structural arrangement and cellular signaling, significant association with kinase, exploring the new target sites and introducing new formulation strategies such as gene modulation, nano-formulations and click chemistry is a prerequisite. In-addition to gene modulation strategies, encapsulated formulation within a nano-carrier for producing promising SOD therapeutic effects, application of click chemistry including bioconjugation and cyclo-addition are the most prominent methods to produce highly efficient SOD formulations. Thus, the present review enlightens the foremost technique which may have better interaction with kinase and other cellular signaling for regulating the physiological process.

Hydrothermally functionalized biocompatible nitrogen doped graphene nanosheet based biomimetic platforms for nitric oxide detection.

Hydrothermal synthesis of nanocomposites is of significant importance, as it affords facile, biocompatible, nontoxic, and economic fabrication. Herein, we report a hitherto unexplored cytocompatible and reusable biomimetic electrochemical sensor based on pyridyl porphyrin functionalized nitrogen doped graphene nanosheets. The porphyrin functionalized nitrogen doped graphene nanosheets (PFNGS) were prepared by a low temperature hydrothermal method via non-covalent strategies with a minimal impact on their physicochemical properties. Owing to their exceptional attributes like operational ease, low cost, portability, and sensitivity, the as-synthesized PFNGS, formed by π-π interactions, were employed for sensing nitric oxide (NO), which is a key regulator of diverse biological processes. Compared to porphyrin and nitrogen doped graphene nanosheets alone, PFNGS exhibited exceptional sensitivity (3.6191 µA µM-1) and remarkable electrocatalytic properties (0.61 V). This clearly outperforms the previously reported modified electrode materials for the electrochemical detection of NO. Cyclic voltammetry (CV) data also suggested that the PFNGS modified electrode possessed an increased reactive surface area, which results in an increase in the number of reactive sites and low charge transfer resistance. These results also demonstrated that the PFNGS modified electrode showed high stability and reproducibility, the limit of detection (LOD) (S/N = 3) of which was estimated to be 1 nM. Our PFNGS were found to be highly biocompatible and could also detect NO released from macrophage cells. This blend of biocompatibility, electrode stability, electrocatalytic activity along with enhanced sensitivity and selectivity makes PFNGS a powerful and reliable nanomaterial for various biomedical applications in complex biological systems.