title: Biodegradable brush-type copolymer modified with targeting peptide as a nanoscopic platform for targeting drug delivery to treat castration-resistant prostate cancer.
abstract: 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.
authors: Shanghai High-Tech United Bio-Technological R&D Co., Ltd., Shanghai 201206, China.
authors: Tao
authors: T
authors: Liu
authors: Department of Emergency, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. Electronic address: qianxiahuang@sina.com.
authors: Qianxia
authors: Q
authors: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D008689:Methacrylates; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols
keywords: 4-dimethylaminopyridine; Biodegradable polymers; Bufalin; Castration-resistant prostate cancer (CRPC); N,N′-dicyclohexyl- carbodiimide; N-hydroxysuccinimide; benzyl 2-methyl-2-(((propylthio) carbonothioyl)thio) propanoate; benzyl alcohol; bufalin, 3-((2-(methacryloyloxy)ethyl)thio)propanoic acid; oligo(ethylene glycol) monomethyl ether methacrylate; triethylamine; ε-caprolactone