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

Abstract

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.