Rapid Polymer Conjugation Strategies for the Generation of pH-Responsive, Cancer Targeting, Polymeric Nanoparticles

The combination of controlled living polymerizationin association with rapid and highly efficient macromolecule conjugationstrategies provides a powerful tool for the synthesis of novel polymeric materials. Here functional block copolymers were rapidly and quantitatively conjugatedusing an efficient reaction between polymers containing a phenolic group and the 4-phenyl-3H- 1,2,4-triazole-3,5(4H)-dione (PTAD) moiety and used to generate nanoparticles that encapsulated drugs. pH responsive amphiphilic block copolymers, which self-assembleinto nanoparticles, were fabricated using our novel polymer conjugationstrategy with the resulting system designed to promote drug release within the acidic milieu of the cancer microenvironment. The conjugationstrategy also enabled the direct tagging of the nanoparticles with a range of fluorophores, targeting assets, or both with cargo release demonstrated in cancer cells.