title: 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.
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research (IISER)-Pune, Dr Homi Bhabha Road, Pune - 411008, Maharashtra, India. jayakannan@iiserpune.ac.in.
authors.forename: P S
authors.initials: PS
authors.lastname: Pramod
authors.forename: Ruchira
authors.initials: R
authors.lastname: Shah
authors.forename: Sonali
authors.initials: S
authors.lastname: Chaphekar
authors.forename: Nagaraj
authors.initials: N
authors.lastname: Balasubramanian
authors.forename: Manickam
authors.initials: M
authors.lastname: Jayakannan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis; D004950:Esterases / Q000378:metabolism; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011108:Polymers / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D011134:Polysaccharides; D004317:Doxorubicin; D004950:Esterases; D002166:Camptothecin