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

Weishuo Li, Jin Geng, Helen Titmarsh, Alicia Megia-fernandez, Kev Dhaliwal, Margaret Frame, Mark Bradley

Research output: Contribution to journalArticlepeer-review

Abstract


The combination of controlled living polymerization in association with rapid and highly efficient macromolecule conjugation strategies provides a powerful tool for the synthesis of novel polymeric materials. Here functional block copolymers were rapidly and quantitatively conjugated using 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. Although generic polymeric nanoparticles have limited potential for cancer targeted drug delivery, improved targeting efficiency and controlled release can be mediated by pH. Here pH responsive amphiphilic block copolymers, which self-assemble into nanoparticles, were fabricated using our novel polymer conjugation strategy with the resulting system designed to promote drug release within the acidic milieu of the cancer microenvironment. The conjugation strategy also enabled the direct tagging of the nanoparticles with a range of fluorophores and/or targeting assets, with cargo release demonstrated in cancer cells.
Original languageEnglish
JournalBiomacromolecules
Early online date24 Apr 2018
DOIs
Publication statusE-pub ahead of print - 24 Apr 2018

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