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Biodegradable brush-type copolymer modified with targeting peptide as a nanoscopic platform for targeting drug delivery to treat castration-resistant prostate cancer.

Well-defined amphiphilic tumor-targeting brush-type copolymers, poly(oligo(ethylene glycol) monomethyl ether methacrylate-co-G3-C12)-g-poly(ε-caprolactone) (P(OEGMA-co-G3-C12)-g- PCL), were synthesized by the combination of ring-opening polymerization (ROP), reversible addition-fragmentation transfer (RAFT) polymerization and polymer post-functionalization, in which G3-C12 was castration-resistant prostate cancer (CRPC) targeting peptide. The obtained polymers were then employed for the targeted treatment of CRPC by delivering a hydrophobic anticancer drug (bufalin, BUF). Polymerizable monomer, 3-((2-(methacryloyloxy)ethyl)thio)propanoic acid (BSMA) and PCL-based macromolecular monomer (PCLMA) were synthesized at first. RAFT polymerization of OEGMA, BSMA, and PCLMA afforded amphiphilic brush-type copolymers, P(OEGMA-co-BSMA)-g-PCL. Post-functionalization of the obtained polymers with G3-C12 led to the formation of the final amphiphilic targeting brush-type copolymers, P(OEGMA-co-G3-C12)-g- PCL. In aqueous media, P(OEGMA-co-G3-C12)-g-PCL self-assembles into micelles with a hydrodynamic diameter (Dh) of ∼66.1±0.44nm. It was demonstrated that the obtained micellar nanoparticles exhibited good biocompatibility and biodegradability. Besides, BUF-loaded micellar nanoparticles assembled from P(OEGMA-co-G3-C12)-g-PCL, BUF-NP-(G3-C12), showed a controlled drug release in vitro and improved anticancer efficacy both in vitro and in vivo.

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