A comprehensive study on 2D, 3D and solid tumor environment to explore a multifunctional biogenic nanoconjugate.

Emergence of nanotechnology created a drastic change in the field of cancer therapy due to their unique features in drug delivery and imaging. Polysaccharide based nanoparticles have received extensive attention in recent years as promising nanoparticle mediated drug delivery systems. Polysaccharides are endorsed with versatile merits including high drug encapsulation efficiency, efficient drug protection against chemical or enzymatic degradation, unique ability to create a controlled release and cellular internalization. In the current study, we have fabricated doxorubicin-loaded carboxymethylated PST001 coated iron oxide nanoparticles (DOX@CM-PST-IONPs) for better management of cancer. CM-PST coated iron oxide nanoparticles co-encapsulated with chemotherapeutic drug doxorubicin, can be utilized for targeted drug delivery. Biocompatible and non-toxic nanoconjugates was found to be effective in both 2-D and 3-D cell culture system with efficient cancer cell internalization. The bench-marked potential of CM-PIONPs to produce reactive oxygen species makes it a noticeable drug delivery system to compact neoplasia. These nanoconjugates can lay concrete on a better way for the elimination of cancer spheroids and tumor burden.

Folic acid-appended galactoxyloglucan-capped iron oxide nanoparticles as a biocompatible nanotheranostic agent for tumor-targeted delivery of doxorubicin.

Iron oxide nanoparticles (IONPs) are employed as MRI contrast agents and as effective drug delivery vehicles. However, the limited solubility and biodegradability of these nanoparticles need to be improved for safer biomedical applications. In an attempt to improve the bottlenecks associated with IONPs, the current study focuses on the synthesis of folic acid conjugated, galactoxyloglucan-iron oxide nanoparticles (FAPIONPs), for the loading and controlled release of the encapsulated chemotherapeutic agent doxorubicin (DOX). The as-designed DOX@FAPIONPs induced a dose-dependent increase in cytotoxicity in folate receptor-positive cells through a caspase-mediated programmed cell death pathway while bare DOX demonstrated a non-targeted toxicity profile. Using LC-MS/MS analysis, several major biological processes altered in treated cells, from which, cell cycle, cellular function and maintenance were the most affected. Detailed toxicity studies in healthy mice indicated the absence of any major side effects while bare drugs created substantial organ pathology. Gadolinium-based contrast agents have a risk of adverse effects, including nephrogenic systemic fibrosis overcome by the administration of DOX@FAPIONPs in xenograft mice model. Tumor-targeted biodistribution pattern with a favorable DOX pharmacokinetics will be the driving factor behind the appealing tumor reduction capacity and increased survival benefits demonstrated on solid tumor-bearing mice.

Self-assembled drug loaded glycosyl-protein metal nanoconstruct: Detailed synthetic procedure and therapeutic effect in solid tumor treatment.

Nanotechnology-based drug delivery research has largely focused on developing well efficient localized delivery therapeutic agents to overcome the limitations of non-specificity and toxicity of conventional chemotherapy. Herein, we constructed a nanoplatform based on a self-assembled polysaccharide-protein conjugate to deliver anti-tumor drug doxorubicin and gold nanoparticles (DOX@PST-BSA AuNPs) for cancer therapy. The self-assembled DOX@PST-BSA AuNPs exhibited higher stability and thermal properties which enable them for drug delivery via passive targeting. The fluorescent property of the drug contributes to the self-monitoring of NPs Biodistribution in vitro and in vivo. Furthermore, the NPs showed negligible cytotoxicity and tissue accumulation in normal cells in vivo. Importantly, the NPs could load the anti-tumor drug with high encapsulation efficiency and competently delivered into the tumor microenvironment thereby inhibit tumor growth significantly through apoptotic induction. Notably, DOX@PST-BSA AuNPs exhibits low systemic toxicity and very few side effects in vivo. Based on the explored features, these NPs could serve as a promising multifunctional drug delivery nanoplatform for cancer therapy.

Doxorubicin eluting microporous polysaccharide scaffolds: An implantable device to expunge tumour.

A variety of naturally derived and synthetic biomaterial scaffolds have been investigated as 3D environments for supporting cell growth and can be used to achieve drug delivery with high loading efficiency. Polysaccharides which enhance the tumour-specific drug release are ideal candidates for scaffold preparation in combination with chemotherapeutic agents for the management of solid tumours by local applications. Galactoxyloglucan (PST001) based porous scaffolds (PS) were prepared by crosslinking and freeze drying with a porosity of 90%. FTIR showed the same functional groups as of PST001 with slight peak shifts and 1200% water absorption was observed. Comparing with PBS, macrophage mediated improved degradation up to 40% in 28 days was observed. The scaffold was relatively non toxic towards normal and cancer cells and there was no epithelial mesenchymal transition (EMT) observed. In vitro drug release profile of doxorubicin (DOX)-loaded scaffold (PSD) showed higher release at acidic pH, apparent in tumour microenvironment, than normal physiological pH. In in vitro assays, cell viability was decreased confirming the drug release potential of the scaffold. DLA tumour was significantly reduced with PSD implantation. The excellent biodegradability of the PS overcome the limitations of non-biodegradable systems which support the sustained release of the drug and degrade after a specific time period. The local tumour reduction potential of the PSD embrace immense application in malignant solid tumour management.

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.

Overcoming drug-resistance in lung cancer cells by paclitaxel loaded galactoxyloglucan nanoparticles.

Paclitaxel, an effective chemotherapeutic drug, is insoluble in aqueous solvents and is usually administered with excipients which have side effects. The use of this drug is also limited due to multi-drug resistance. In this study polysaccharide nanoparticles are used in the delivery of chemotherapeutic drug while minimizing side-effects, solubility issues and drug resistance. The use of biopolymers like galactoxyloglucan to synthesize nanoparticle makes it more biocompatible. This study involves the synthesis of PST-PTX nanoparticles using tamarind seed polysaccharide and Paclitaxel by epichlorohydrin crosslinking. The particles were further characterized by Dynamic Light Scattering (DLS), High-resolution transmission electron microscopy (HR-TEM) Fourier Transform Infrared Spectroscopy (FTIR) and UV-Visible spectroscopy. The cytotoxicity of PST-PTX nanoparticles in cancer cell lines and resistant cancer cell lines were determined by MTT assay. The quantitative analysis of cell death was determined by Annexin V dead cell assay, Caspase 3/7 assay and expression of pro-apoptotic protein Bax. The ability of the nanoparticle to overcome multi-drug resistance was evaluated by the expression of multidrug-resistant proteins P-glycoprotein (P-gp) and Breast cancer resistant protein (BCRP) in lung adenocarcinoma resistant cells (A549R). The present study provides evidence for the ability of PST-PTX nanoparticle to overcome multi-drug resistance and cause apoptotic cell death. The particle was found to be more effective than Paclitaxel in causing cell death in resistant cancer cells. Moreover, the particles were found to downregulate the expression of multi-drug resistant proteins P-gp and BCRP in resistant cell lines suggesting the ability of PST-PTX nanoparticles to overcome multi-drug resistance.

Galactomannan endowed biogenic silver nanoparticles exposed enhanced cancer cytotoxicity with excellent biocompatibility.

Galactomannan isolated from the fruit rind of Punica granatum was previously reported to have excellent antioxidant, immunomodulatory and anticancer properties against both human and murine cancer cells. This polysaccharide was proved to be an anticancer agent either alone or as an adjuvant to chemotherapy. An exploration leads to the fabrication of silver nanoparticles with an average size around 30 nm and a negative surface charge of 35.2 mV using this biopolymer which acted both as reducing and capping agent and displayed good stability and biocompatibility. UV-vis spectrum of the aqueous medium containing silver nanoparticles showed an absorption peak at around 440 nm. The nanoparticles displayed an upgraded and selective cytotoxicity towards human adenocarcinoma, colorectal carcinoma and hepatocellular carcinoma cells. The induction of cancer cell toxicity was proved to be through the induction of programmed cell death pathway mediated with the active involvement of caspases. The significant anti-metastatic properties will further favour the safer in vivo application of these silver nanoparticles against neoplasia. The nontoxic nature of polysaccharide endowed the resultant silver nanoparticles with excellent biocompatibility towards red blood cells and extended the biomedical potential of this candidate. Hence, the surfactant-free green method mediated orchestration of biogenic silver nanoparticles resembled a potential theransonstic nano-construct with synergistic anticancer and immunomodulatory potential in a single platform.

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.