Self-assembling poly(ethylene glycol)-block-polylactide-cabazitaxel conjugate nanoparticles for anticancer therapy with high efficacy and low in vivo toxicity.

Traditional approaches used for transforming hydrophobic anticancer drugs into therapeutically available nanoparticles heavily rely on the noncovalent formulation of drugs within amphiphilic copolymers. However, these nanotherapies have not yet shown the expected favorable clinical outcomes in cancer patients, presumably due to their insufficient stability. To solve this dilemma, we conceive a new class of nanotherapies assembled with polymeric prodrugs that maintain pharmacological activity while substantially alleviate the drug toxicity in animals. By exploiting methoxypoly(ethylene glycol)-block-poly(D, L-lactic acid) (mPEG-PLA) as a promoiety, cabazitaxel is tethered to the terminus of the PLA fragment via a hydrolysable ester linkage. These conjugates recapitulate the self-assembly to produce colloidal stable nanotherapies. In a xenograft model of prostate cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose. Our results suggest that a hydrophobic and highly toxic drug can be rationally converted into a pharmacologically efficient and self-deliverable nanotherapy.