The Drug-Initiated Method: A Convenient Approach for the Synthesis of Efficient Polymer Prodrug Nanoparticles

Herein is reported the synthesis of new amphiphilic polymer prodrug nanoparticles by controlled radical polymerization (CRP) and their biological evaluation against cancer. The methodology, termed 'drug initiated', consisted in growing a short hydrophobic polymer chain from a pre-modified hydrophilic drug under CRP conditions. It resulted in well-defined amphiphilic drug-polymer conjugates able to form self-stabilized prodrug nanoparticles with significant anticancer activity in vitro and in vivo. This was illustrated by the use of the anticancer drug gemcitabine (Gem) which was functionalized with CRP moieties for the synthesis of two different biorelevant polymer promoieties: polyisoprene and a polymethacrylate with pending squalene as a natural lipid.