Synthesis the Stimuli-Responsive Targated Unimolecular Micelle Carrier and Study the Application for Drug Controlled Release

Cancer has been the major loading cause of mortality in the world and the burden of cancer cases keeps rapidly growing due to the aging population. In the last few decades, chemotherapy has emerged as a preferential and effective method to treat cancer. Polymeric micelles can be used as an efficient carrier to enhance the therapeutic efficacy and reduce side effects of therapeutic drugs, especially those with poor solubility. However, classical polymeric micelles (multi-molecular micelles) represent thermodynamic aggregations of amphiphilic macromolecules above their critical micelle concentration (CMC), and they will disassemble into free polymeric chain once the polymer concentration is below CMC. This drawback will heavily hinder their in vivo drug delivery applications. In contrast, uni-molecular micelles composed of single non-linear polymers such as star-like or hyperbranched polymers show stable micellar integrity and controllable size, providing a straight forward resolution to tackle this issue. This unique property of uni-molecular micelles are typically small enough to prevent accumulation in the spleen, liver and yet large enough to show renal filtration.In this project, a novel star-like organic- inorganic hybrid copolymer POSS-(-S-S-MPEG/Galactose/HA)8 will be synthesized via the thio-ene click, ring-opening polymerization (ROP) and nucleophilic substitution reactions. The prepared copolymer features a redo-cleavable disulfide linkage between the hydrophilic MPEG/Galactose/HA and hydrophobic polyhedral oligomeric silsequioxane (POSS) core. Due to the unique architecture, this copolymer can self-assemble into uni-molecular micelles. The labile disulfide bonds in the block copolymer can be cleaved under reducing environments. Additional, we will study the thermal properties of stark-like material, the micelle characteristic, and cellular uptake.

Project ID:PB10708-2102
External Project ID:MOST107-2221-E182-015