Semi-interpenetrating nanosilver doped polysaccharide hydrogel scaffolds for cutaneous wound healing.

The extensive advancement with novel wound dressing materials functionalized with desirable properties, often touted as a panacea for cuts and burns afflicting various pathologies. However, it would indeed be a hard task to isolate any such material which perfectly fits the needs of any biomedical issue at hand. Biocompatibility, biodegradability as well as non-toxicity of natural polysaccharide served as a versatile and tunable platform for designing natural polysaccharide based scaffolds as an attractive tool in tissue engineering with a greater degree of acceptability. In this regard, we aimed to fabricate a semi interpenetrating hydrogel via exploiting the nontoxic and immune-stimulatory nature of galacto-xyloglucan (PST001) which was further doped with silver nanoparticles to formulate SNP@PST. The wound healing potential of SNP@PST was then studied both with in vitro and preclinical mice models. The current study gives a formulation for cost effective preparation of polysaccharide hydrogels using acrylamide crosslinking with improved biocompatibility and degradability. Wound healing studies in mice proved the efficiency of gels for the clinical application wherein the incorporation of nanosilver greatly enhanced the antimicrobial activity.

Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells.

Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.

Anticancer activity of galactoxyloglucan polysaccharide-conjugated doxorubicin nanoparticles: Mechanistic insights and interactome analysis.

Toxicity associated with chemotherapeutic drugs such as doxorubicin (Dox), is one of the major obstacles that is currently affecting patients. PST-Dox (Galactoxyloglucan, PST001-conjugated Dox) nanoparticles were synthesized by encapsulating Dox with polysaccharide PST001, isolated from Tamarindus indica (Ti) by ionic gelation with tripolyphosphate (TPP). Herein, we demonstrate a detailed mechanistic and interactome network analysis that is specific to PST-Dox action in cancer cells and normal lymphocytes. Our results show that PST-Dox is superior to its parental counterparts, exhibiting a greater cytotoxicity by the induction of apoptosis against a wide variety of cancers by enhanced cellular uptake of Dox from the nanoparticle conjugates. Also, PST-Dox nanoparticles were non-toxic to normal lymphocytes with limited immunostimulatory effects up to certain doses. Elucidation of molecular mechanism by whole genome microarray in cancer cells and lymphocytes revealed that a large number of genes were dysregulated specifically in cancer cells. Specifically, a unique target gene EGR1, contextually determined translational activation of P53 in the cancerous and non-cancerous cells. Most of the key downregulated genes were tyrosine kinases, indicating the potential inhibitory action of PST-Dox on tyrosine kinase oncogenic pathways. Western blotting of proteins corresponding to the genes that were altered at the genomic level was very well correlated in the majority of them, except in a few that demonstrated post-transcriptional modifications. The important findings and highly disciplined approaches highlighted in the present study will speed up the therapeutic potential of this augmented nanoparticle formulation for more robust clinical studies and testing in several cancers.

Serum levels of copper, zinc, iron and ceruplasmin in oral leukoplakia and squamous cell carcinoma.

Trace elements have been extensively studied in recent years to assess whether they have any modifying effects in the etiology of cancer. In the present study serum levels of copper, zinc, ceruloplasmin, total iron and total protein were estimated in 92 patients with oral leukoplakia and squamous cell carcinoma and 45 age and sex matched controls. Copper was significantly increased in oral leukoplakia and cancer in both sexes. The level of zinc decreased significantly only in male patients with leukoplakia and cancer. Copper zinc ratio was found significantly elevated in oral leukoplakia and cancer. A marked increase in serum ceruloplasmin was seen in oral leukoplakia and cancer in both sexes. A significant decrease of serum total iron and proteins were observed only in carcinomas. These findings suggest that reduction in the serum total iron and total protein may be due to malnutrition caused, on its turn, by tumour burden. Serum ceruloplasmin level and copper-zinc ratio demonstrated significant differences in the patients of both sexes from those of controls, while, comparing leukoplakia with cancer, a significant difference is only observed in male patients. Thus, the present study shows that these factors have diagnostic value only in differentiating malignancies from normal and a little value as biomarkers of disease progression. However, the exact mechanism responsible for the alteration of these factors in oral lesions is still not clear and a detailed study on large sample size is therefore needed.