Tetraphenylsilane-Cored Star-Shaped Amphiphilic Block Copolymers for pH-Responsive Anticancer Drug Delivery

Four-arm star-shaped poly[2-(diethylamino)ethyl methacrylate]-b-poly[2-hydroxyethyl methacrylate]s block copolymers using tetraphenylsilane (TPS) as a core with adjustable arm lengths are synthesized through two-step atom transfer radical polymerizations. For comparison, a linear block copolymer with similar molecular weight is also prepared. The assembled star-shaped copolymer micelles exhibit sizes of 102-139 nm and critical micelle concentrations of 1.49-3.93 mg L-1. Moreover, the bulky and rigid TPS core is advantageous for propping up the four star-shaped arms to generate large intersegmental space. As a result, the drug-loading capacity in the micelles is up to 33.97 wt%, much surpassing the linear counterpart (8.92 wt%) and the previously reported star-shaped copolymers prepared using pentaerythritol as the core. Furthermore, the micelles show sensitive pH-responsive drug release when the pH changes from 7.4 to 5.0. The in vitro cytotoxicity to Hela cells indicates that the doxorubicin (DOX)-loaded micelles have similar anticancer activity to the pristine DOX. The combination of excellent micelle stability, high drug-loading, sensitive pH response, and good anticancer activity endows the copolymers with promising application in drug control delivery for anticancer therapy.