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 ( D h ) of ∼66.1   ±   0.44   nm. 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.