Amphiphilic
polycarbonate/PEG copolymer with a star-like architecture was designed to facilitate a unique supramolecular transformation of
micelles to vesicles in aqueous
solution for the efficient delivery of anticancer drugs. The star-shaped amphipilic block copolymer was synthesized by initiating the ring-opening polymerization of
trimethylene carbonate (TMC) from
methyl cholate through a combination of
metal-free organo-catalytic living ring-opening polymerization and post-polymerization chain-end derivatization strategies. Subsequently, the self-assembly of the star-like
polymer in aqueous
solution into nanosized vesicles for anti-
cancer drug delivery was studied. DOX was physically encapsulated into vesicles by dialysis and
drug loading level was significant (22.5% in weight) for DOX. Importantly, DOX-loaded nanoparticles self-assembled from the star-like copolymer exhibited greater kinetic stability and higher DOX loading capacity than
micelles prepared from
cholesterol-initiated diblock analogue. The advantageous disparity is believed to be due to the transformation of
micelles (diblock copolymer) to vesicles (star-like block copolymer) that possess greater core space for
drug loading as well as the ability of such supramolecular structures to encapsulate DOX. DOX-loaded vesicles effectively inhibited the proliferation of 4T1, MDA-MB-231 and BT-474 cells, with IC50 values of 10, 1.5 and 1.0mg/L, respectively. DOX-loaded vesicles injected into 4T1
tumor-bearing mice exhibited enhanced accumulation in
tumor tissue due to the enhanced permeation and retention (EPR) effect. Importantly, DOX-loaded vesicles demonstrated greater
tumor growth inhibition than free DOX without causing significant
body weight loss or
cardiotoxicity. The unique ability of the star-like copolymer emanating from the
methyl cholate core provided the requisite modification in the block copolymer interfacial curvature to generate vesicles of high loading capacity for DOX with significant kinetic stability that have potential for use as an anti-
cancer drug delivery carrier for
cancer therapy.