Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 54, Issue 3, Pages 1002-1006Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201409293
Keywords
cancer therapy; nanoparticles; polymer-drug conjugates; polymerizable prodrugs; ring-opening polymerization
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Funding
- NIH [R01-EB 000188, R01-DK092665]
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The synthesis of polymer-drug conjugates from prodrug monomers consisting of a cyclic polymerizable group that is appended to a drug through a cleavable linker is achieved by organocatalyzed ring-opening polymerization. The monomers polymerize into well-defined polymer pro-drugs that are designed to self-assemble into nanoparticles and release the drug in response to a physiologically relevant stimulus. This method is compatible with structurally diverse drugs and allows different drugs to be copolymerized with quantitative conversion of the monomers. The drug loading can be controlled by adjusting the monomer(s)/initiator feed ratio and drug release can be encoded into the polymer by the choice of linker. Initiating these monomers from a poly(ethylene glycol) macroinitiator results in amphiphilic diblock copolymers that spontaneously self-assemble into micelles with a long plasma circulation, which is useful for systemic therapy.
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