Polysaccharide nano-vesicular multidrug carriers for synergistic killing of cancer cells

Abstract

Multi-drug delivery based on polymer nano-scaffolds is an essential protocol to be developed for better administration of anticancer drugs to enhance their therapeutic efficacies against cancer cells. Here, we report dual delivery polysaccharide nano-vesicles that are capable of loading and delivering both water soluble and water insoluble drugs together in a single polymer scaffold. The selective rupture of the nano-vesicular assembly under intracellular enzyme conditions allowed the simultaneous delivery of a hydrophobic drug camptothecin (CPT) and hydrophilic drug doxorubicin (DOX) supporting their synergistic killing of breast and colon cancer cells. The polysaccharide nano-vesicles have allowed us to address a few important questions regarding the need for multiple drug administration in cancer cells including (a) the role of simultaneous drug release, (b) antagonistic versus synergistic effects of drug combinations and (c) how these are affected by the ratio of drugs. Further, evaluation of the role of caveolae in endocytosis of these polymer scaffolds was also made. The vesicular scaffolds were found to preserve and deliver DOX resulting in 50-60% better killing of cancer cells than the free drug. Additionally, dual loaded nano-vesicles when compared to drug cocktails with individual drugs in separate nano-vesicles (at comparable molar ratios) suggest the relative drug concentration following release and mode of delivery to be both important in cancer cell killing. Results from these experiments have revealed newly developed polysaccharide nano-vesicles loaded with DOX and CPT drugs as potential candidates for improved breast cancer cell killing. Thus, these custom-designed polysaccharide nano-vesicles provide a new perspective on multi-anticancer drug delivery systems and their efficacy.

Dual stimuli polysaccharide nanovesicles for conjugated and physically loaded doxorubicin delivery in breast cancer cells

“…42 Briefly, 100 mg of DEX-IM-5 and 2 mg of DOX·HCl were dissolved in 3 mL of DMSO and stirred moderately at 25°C under dark conditions. Self assembly of DEX-IM-5 was induced by the slow injection of 3 mL of PBS ( pH 7.4) into the above solution.…”

Enzymatically triggered rupture of polymersomes

“…1, 2 Due to their mechanical stability, 1, 3, 4 capacity for additional functionalization, and lower permeability, 5 polymersomes offer significant advantages over other bilayer vesicle in encapsulating and transporting enzymes, 6, 7 proteins, 8, 9 drugs, 9–14 and biomedical imaging and diagnostics. 15–18 Furthermore, the interior compartment of polymersomes has been engineered to serve as a micro-environment for protein expression, 8 gene expression, 19 and enzymatic reaction.…”

“…Somatologically favorable enzymatic reactions also have been used to control the release of encapsulants from polymersomes. 14, 17, 18, 23 Although these strategies have successfully shown the disruption of polymersomes to trigger the release of encapsulants, few studies have demonstrated the ability to tailor the rate of rupture/release using an enzyme cascade which can be readily controlled by the concentration of substrate.…”

A review of solute encapsulating nanoparticles used as delivery systems with emphasis on branched amphipathic peptide capsules

“…Dextran, chitin, chitosan and their derivatives have been investigated for their use as drug carriers. Most of the vesicles in this category are modified polysaccharides adducted with either small (trimethyl-) 141,142 or larger (3-pentadecylphenol-) 143,144 hydrophobic groups to render them amphipathic. Chitosan derived polymer vesicles are the most studied in this category.…”