Research Outline

Nanomedicine has already been recognized as a translational technology for efficient delivery of the chemotherapeutics to the diseased site, minimizing therapy related side-effects, which eventually ensures better quality of life (QOL) for the patient.  In our laboratory, at iCONM, with the state-of-the-art research infrastructure, we focus on polymeric micelle based nanomedicines to treat intractable cancers. Polymeric micelle, a self-assembling nano-structure of amphiphilic block-copolymers, takes advantage of the "enhanced permeability and retention" (EPR) effect (that is based on the pathophysiological characteristics of solid tumor tissues) to preferentially penetrate and accumulate in solid tumors. In addition to EPR mediated selective tumor accumulation, precise control of the size of the nano-carriers, surface modification by disease-targeting ligands and engineered stimuli-triggered drug release mechanism can further enhance tumor selective delivery of therapeutics and thereby facilitate the interaction between loaded-drug and target cells or tissues. Confirming the practical application of these research strategies, several polymeric micelles incorporating the anticancer agents paclitaxel, SN-38, cisplatin, 1,2-diaminocyclohexane platinum(II) (DACHPt) and epirubicin are being evaluated clinically (paclitaxel and cisplatin loaded micelles have already progressed to the third phase). We demonstrated (as shown in the above illustrations) that DACHPt incorporated micelle with strategically controlled size, is capable of bypassing the cytoplasmic detoxification mechanisms by selective dissociation within the late-endosome and thus releases drug close to the target site (nucleus in this case); ultimately overcoming oxaliplatin resistance in tumors and ensuring higher antitumor activity in pancreatic tumor model. Furthermore, our researchers have also successfully accomplished to encapsulate therapeutic small interfering ribonucleic acid (siRNA) inside a ligand-decorated polymeric micelle system that conjures therapeutic activity toward solid tumors following intravenous (IV) administration. Comprehending that cancer stem cells (CSCs) with self-renewal capacity are the root cause of cancer recurrence and drug resistance, we are currently directing our research for methodical application of polymeric micellar nanomedicines to target and eradicate CSCs and thus to reinvigorate the global effort against an enduring challenge in the field of oncology.