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

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• 作者：Tao Liu^a ; Qianxia Huang^b ; ^{qianxiahuang@sina.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：oligo(ethylene glycol) monomethyl ether methacrylate ; ε-caprolactone ; benzyl alcohol ; bufalin ; 3-((2-(methacryloyloxy)ethyl)thio)propanoic acid ; N ; N&prime ; -dicyclohexyl- carbodiimide ; 4-dimethylaminopyridine ; N-hydroxysuccinimide ; benzyl 2-methyl-2-(((propylthio) carbonothioyl)thio) propanoate ; triethylamine
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：25 September 2016
• 年：2016
• 卷：511
• 期：2
• 页码：1002-1011
• 全文大小：2451 K

文摘

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.