Graphene oxide-reinforced pectin/chitosan polyelectrolyte complex scaffolds.

Three-dimensional (3D) porous scaffolds based on graphene oxide (GO) incorporated pectin/chitosan polyelectrolyte complex (PCGO) were prepared by the freeze-drying technique. The chemical composition and microstructure of the prepared PCGO scaffolds were studied by FTIR and XRD analysis. The presence of GO and its uniform distribution within the polymer matrix was confirmed by Raman spectroscopy and confocal Raman mapping analysis, respectively. TGA analysis revealed that the addition of GO improves the thermal stability of the pectin/chitosan complex. SEM analysis confirmed the uniform pore distribution of PCGO scaffolds. Moreover, it showed that the pore size of the scaffolds was decreased with the increase in GO content. Among the developed PCGO scaffolds, the scaffolds with 1 wt.% of GO presented the improved hydrophilicity by exhibiting the water swelling degree of 2004%, water retention capacity of 1101% and water contact angle (WCA) of 21°. In addition, these scaffolds presented better compressive strength (∼283 kPa) and resistance towards lysozyme-mediated degradation. The PCGO scaffolds presented an acceptable level of bio-and hemocompatibility and GO concentration-dependent cell attachment ability. These results demonstrate the suitability of PCGO scaffolds for tissue engineering.

Three-dimensional porous scaffolds based on agarose/chitosan/graphene oxide composite for tissue engineering.

Three-dimensional (3D) porous scaffolds based on agarose/chitosan/graphene oxide (ACGO) composite were prepared by the freeze-drying technique. The prepared scaffolds were characterized by FTIR, XRD and SEM analysis. The effect of graphene oxide (GO) on the physicochemical and biological properties of the composite scaffolds was evaluated in terms of porosity, swelling, water retention, compressive strength, enzymatic degradation, cytotoxicity and cell attachment behaviors. The ACGO composite scaffolds exhibited the well-defined interconnected pores with rough surface morphology. The porosity, swelling, water retention ability and compressive strength of the composite scaffolds increased with the increase in GO content, while the degradation rate of the scaffolds decreased with the addition of GO. The composite scaffolds showed adequate hemocompatibility and Vero cell proliferation ability. Cell attachment studies demonstrated that GO present in the composite scaffolds provided a favorable environment for cell attachment and proliferation. These results suggest that ACGO composite scaffolds could be reliable and appropriate for tissue engineering applications.

Preparation and characterization of three-dimensional scaffolds based on hydroxypropyl chitosan-graft-graphene oxide.

Hydroxypropyl chitosan (HPCH), a water soluble derivative of chitosan, is widely considered for tissue engineering and wound healing applications due to its biocompatibility and biodegradability. Graphene oxide (GO) is a carbon-based nanomaterial which is capable of imparting desired properties to the scaffolds. Hence, the integration of GO into HPCH could allow for the production of HPCH-based scaffolds with improved swelling character, mechanical strength, and stability aimed at being used in tissue engineering. In this study, hydroxypropyl chitosan-graft-graphene oxide (HPCH-g-GO) with varying GO content (0.5, 1, 3 and 4wt.%) was prepared using HPCH and GO as a tissue engineering scaffold material. The formation of HPCH-g-GO was confirmed by FTIR and XRD analysis. Using the HPCH-g-GO as a matrix material and glutaraldehyde as a crosslinking agent, the three dimensional (3D) porous scaffolds were fabricated by the freeze-drying method. The HPCH-g-GO scaffolds exhibited uniform porosity as observed in SEM analysis. The pore size and porosity reduced as the content of GO was increased. These scaffolds presented good swelling capacity, water retention ability, mechanical strength and in vitro degradation properties. The HPCH-g-GO scaffolds irrespective of their GO content demonstrated good cell viability when compared to control. Altogether, these results suggest that HPCH-g-GO scaffolds can be used as potential tissue engineering material.

Prospects of chitosan-based scaffolds for growth factor release in tissue engineering.

Tissue engineering is concerned about the rejuvenation and restoration of diseased and damages tissues/organs using man-made scaffolds that mimic the native environment of the cells. In recent years, a variety of biocompatible and biodegradable natural materials is employed for the fabrication of such scaffolds. Of these natural materials, chitosan is the most preferred one as it imitates the extracellular matrix (ECM) of the cells. Moreover, chitosan-based materials are pro-angiogenic and have antibacterial activity. These materials can be easily fabricated into the desired shape of the scaffolds that are suitable for tissue support and regeneration. Growth factors are small proteins/peptides that support and enhance the growth and differentiation of cells into a specific lineage. It has been observed that scaffolds capable of delivering growth factor promote tissue repair and regeneration at a faster rate when compared to scaffolds without growth factor. The present review focuses on the recent developments on chitosan-based scaffolds for the delivery of growth factors thereby improving and enhancing tissue regeneration.

Peptides to Target Tumor Vasculature and Lymphatics for Improved Anti-Angiogenesis Therapy.

Cancer has become one of the leading causes of increased mortality. The currently employed diagnostic and therapeutic modality offers only minimal specificity towards cancerous cells and affects normal healthy cells. Targeted drug delivery systems have shown an improved efficiency in the diagnosis and treatment of various cancers, as the targeted molecules specifically reach the tumor cells without exerting any undesirable effects on the normal healthy cells. Recent findings have shown that disruption of blood vasculature and lymphatics is efficient in treating various cancers. As these vessels supply nutrient and oxygen, remove wastes and help in the metastasis; therapeutic agents targeting them will be highly useful. Of the various ligands used for targeting blood vasculature and lymphatics, peptides possess great advantage over other molecules. This review article is aimed at focusing the recent findings and developments on the peptides as targeting ligands for the improved anti-angiogenesis therapy.

Development of nanotheranostics against metastatic breast cancer--A focus on the biology & mechanistic approaches.

Treatment for metastatic breast cancer still remains to be a challenge since the currently available diagnostic and treatment strategies fail to detect the micro-metastasis resulting in higher mortality rate. Moreover, the lack of specificity to target circulating tumor cells is also a factor. In addition, currently available imaging modalities to identify the secondaries vary with respect to various metastatic anatomic areas and size of the tumor. The drawbacks associated with the existing clinical management of the metastatic breast cancer demands the requirement of multifunctional nanotheranostics, which could diagnose at macro- and microscopic level, target the solid as well as circulating tumor cells and control further progression with the simultaneous evaluation of treatment response in a single platform. However, without the understanding of the biology as well as preferential homing ability of circulating tumor cells at distant organs, it is quite impossible to address the existing challenges in the present diagnostics and therapeutics against the breast cancer metastasis. Hence this review outlines the severity of the problem, basic biology and organ specificity with the sequential steps for the secondary progression of disease followed by the various mechanistic approaches in diagnosis and therapy at different stages.

Snake venom derived molecules in tumor angiogenesis and its application in cancer therapy; an overview.

Snake venom is a complex mixture of biologically and pharmacologically active components, comprising hydrolytic enzymes, non-enzymatic proteins/peptides, and small amounts of organic and inorganic molecules. The venom components are known to vary with geographic location, season, species and age of the snakes. The role of the venom in the snake is not primarily for self-defense, but in prey immobilization and its subsequent digestion. Hence, several digestive enzymes in venoms, in addition to their hydrolytic activity have evolved to interfere in diverse physiological processes that help in the immobilization of prey/victim. As snake components are capable of modulating the physiological response of envenomated prey/victim, they show promise as potential pharmacological tools, as drug leads and in diagnostic applications. This, in a practical sense to be a reality has to be linked to the advances in toxinology that provide investigators with an understanding of the pharmacodynamics of toxins together with improved understanding of the etiology of many human diseases and identification of potential sites for therapeutic intervention. This review aims at providing an overview on snake venom toxins and their derivatives that have potential anti-angiogenic effects for cancer treatment. Some of the anti-angiogenic components of snake venom like Snake venom metalloproteinases (SVMPs), Disintegrins, Phospholipases A2 (PLA2), CType Lectins (CLP), Vascular Apoptosis inducing Proteins (VAP) and L-Amino Acid Oxidases (LAAO) are discussed. This review aims at giving an overall view of these molecules and their mechanism of action as an effective antiangiogenic agent towards the treatment of cancer.

Homology modeling, molecular dynamics and atomic level interaction study of snake venom 5' nucleotidase.

5' Nucleotidase (5' NUC) is a ubiquitously distributed enzyme known to be present in snake venoms (SV) that is responsible primarily for causing dysregulation of physiological homeostasis in humans by inducing anticoagulant effects and by inhibiting platelet aggregation. It is also known to act synergistically with other toxins to exert a more pronounced anti-coagulant effect during envenomation. Its structural and functional role is not yet ascertained clearly. The 3D structure of snake venom 5' nucleotidase (SV-5' NUC) is not yet known and was predicted by us for the first time using a comparative homology modeling approach using Demansia vestigiata protein sequence. The accuracy and stability of the predicted SV-5' NUC structure were validated using several computational approaches. Key interactions of SV-5' NUC were studied using experimental studies/molecular docking analysis of the inhibitors vanillin, vanillic acid and maltol. All these inhibitors were found to dock favorably following pharmacologically relevant absorption, distribution, metabolism and excretion (ADME) profiles. Further, atomic level docking interaction studies using inhibitors of the SV-5' NUC active site revealed amino acid residues Y65 and T72 as important for inhibitor-(SV-5' NUC) interactions. Our in silico analysis is in good agreement with experimental inhibition results of SV-5' NUC with vanillin, vanillic acid and maltol. The present study should therefore play a guiding role in the experimental design of new SV-5' NUC inhibitors for snake bite management. We also identified a few pharmacophoric features essential for SV-5' NUC inhibitory activity that can be utilized further for the discovery of putative anti-venom agents of therapeutic value for snake bite management.