Next Generation Multiresponsive Nanocarriers for Targeted Drug Delivery to Cancer Cells.

C-H bond activation of 2-methoxyethylamino-bis(phenolate)-yttrium catalysts allowed the synthesis of BAB block copolymers comprised of 2-vinylpyridine (2VP; monomer A) and diethylvinylphosphonate (DEVP; monomer B) as the A and B blocks, respectively, by rare-earth-metal-mediated group-transfer polymerization (REM-GTP). The inherent multi-stimuli-responsive character and drug-loading and -release capabilities were observed to be dependent on the chain length and monomer ratios. Cytotoxicity assays revealed the biocompatibility and nontoxic nature of the obtained micelles toward ovarian cancer (HeLa) cells. The BAB block copolymers effectively encapsulated, transported, and released doxorubicin (DOX) within HeLa cells. REM-GTP enables access to previously unattainable vinylphosphonate copolymer structures, and thereby unlocks their full potential as nanocarriers for stimuli-responsive drug delivery in HeLa cells. The self-evident consequence is the application of these new micelles as potent drug-delivery vehicles with reduced side effects in future cancer therapies.