We report on the design of a new class of polymer prodrug nanocarriers by using the "drug-initiated" method, which consists in the controlled growth of vinyl polymers from anticancer drug-bearing initiators to prepare well-defined and high drug content polymer prodrug nanoparticles with in vitro and in vivo anticancer activity. This method is robust and versatile as was applied to different drugs including Gemcitabine, Cladribine and Paclitaxel, to different polymers and to different drug/polymer linkers to adjust the drug release kinetics and thus the cytotoxicity. Fluorescent polymer prodrug nanocarriers can also be produced in a similar fashion from a fluorescent dye-bearing initiator. This approach was further developed to yield heterotelechelic polymer prodrugs for drug delivery, imaging and combination therapy. We also present our recent achievements to confer degradability to vinyl polymers by using controlled radical ring-opening polymerization (rROP) using cyclic ketene acetal (CKA) monomers. In particular, 2-methylene-4-phenyl-1,3-dioxolane (MPDL) was copolymerized with oligo(ethylene glycol) methyl ether methacrylate (OEGMA) or methyl methacrylate (MMA) by NMP to produce well-defined, non-cytotoxic and degradable copolymers. This approach was eventually applied to the "drug-initiated" synthesis of degradable polymer prodrug nanocarriers with tuneable cytotoxicity towards cancer cells (Figure).

Polymer prodrug nanocarriers for anticancer therapy

2019 Spring National Meeting

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