Synthesis of next generation dual-responsive cross-linked nanoparticles and their application to anti-cancer drug delivery.

Rare earth metal-mediated group transfer polymerisation enables the synthesis of previously inaccessible block copolymers of 2-vinylpyridine, diethyl vinylphosphonate and the new diallyl vinylphosphonate monomer. This precision polymerisation and the selective cross-linking of allyl side groups via thiol-ene click chemistry leads to the formation of well-defined dual-responsive nanoparticles. We demonstrate that these next generation nanocarriers are pH- and temperature-responsive and are capable of efficiently delivering doxorubicin into the nucleus of cancer cells. High anti-cancer activity could be demonstrated via cytotoxicity tests on breast cancer (MCF-7) and cervical cancer (HeLa) cells. These results validate this modular synthesis route as an ideal platform for the development of sophisticated nanocarriers for future drug delivery applications.

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.