Self-stabilized, hydrophobic or PEGylated paclitaxel polymer prodrug nanoparticles for cancer therapy

Facile derivatization of paclitaxel (Ptx) and subsequent "drug-initiated" synthesis of well-defined Ptx-polymer prodrugs was performed from nitroxide-mediated polymerization or reversible addition-fragmentation chain transfer polymerization. Short polyisoprene (M-n = 2640-4310 g mol(-1), D similar to 1.1) or poly[(oligo(ethylene glycol) methyl ether methacrylate)] (M-n = 5580-7530 g mol(-1), D similar to 1.2) chains were grown from Ptx in a controlled fashion and enabled, for the first time, the formation of either self-stabilized, all-hydrophobic Ptx-polymer prodrug nanoparticles or their PEGylated counterparts. They exhibited average diameters in the 110-235 nm range, great colloidal stability in PBS and cell culture medium, high drug loadings (up to 32 wt%) and cytotoxicity similar to that of the parent drug on three different cancer cell lines (A549, L1210 and MCF-7). This versatile approach is expected to provide more potent anticancer nanocarriers and rejuvenate the development of Ptx-based nanomedicines.