title: Disulfide-Linked Amphiphilic Polymer-Docetaxel Conjugates Assembled Redox-Sensitive Micelles for Efficient Antitumor Drug Delivery.
abstract: Here, we prepared novel redox-sensitive drug delivery system based on copolymer-drug conjugates methoxy poly(ethylene glycol)-poly(γ-benzyl l-glutamate)-disulfide-docetaxel (mPEG-PBLG-SS-DTX) to realize the desirable cancer therapy. First, copolymers of methoxy poly(ethylene glycol)-poly(γ-benzyl l-glutamate) (mPEG-PBLGs) with different molecular weight (mPEG2000-PBLG1750 and mPEG5000-PBLG1750) were synthesized via the ring open polymerization (ROP) of 5-benzyl-l-glutamate-N-carboxyanhydride (γ-Bzl-l-Glu-NCA) initiated by monoamino-terminated mPEG (mPEG-NH2). Then, the docetaxel (DTX) was conjugated to the block polymers through a linkage containing disulfide bond to obtain mPEG-PBLG-SS-DTXs, including mPEG2000-PBLG1750-SS-DTX and mPEG5000-PBLG1750-SS-DTX. The obtained copolymer-drug conjugates mPEG2000-PBLG1750-SS-DTX and mPEG5000-PBLG1750-SS-DTX could self-assemble into nanosized micelles in aqueous environment via dialysis method with a low critical micelle concentration (CMC, 3.98 and 6.94 μg/mL, respectively). The size of the micelles was approximately 101.3 and 148.9 nm, respectively, with a narrow size distribution. They released approximately 40% DTX in a sustained way in the presence of 50 mM DTT after 120 h in comparison with only approximately 10% DTX released from micelles in the absence of DTT. The high cytotoxicity was identified for mPEG-PBLG-SS-DTXs micelles against MCF-7/ADR and A549 cells, and the IC50 of mPEG-PBLG-SS-DTXs micelles against MCF-7/ADR for 24 h was roughly a 15th of the value of free DTX. Moreover, the mPEG-PBLG-SS-DTXs micelles could be efficiently uptaken by MCF-7/ADR and A549 cells. Thus, the present constructed mPEG-PBLG-SS-DTXs micelles were very promising for effective cancer therapy.
authors.affiliation: School of Pharmaceutical Science, Shandong University , 44 West Wenhua Road, Jinan, Shandong Province 250012, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science, Shandong University , 44 West Wenhua Road, Jinan, Shandong Province 250012, People's Republic of China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science, Shandong University , 44 West Wenhua Road, Jinan, Shandong Province 250012, People's Republic of China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: He
authors.affiliation: School of Pharmaceutical Science, Shandong University , 44 West Wenhua Road, Jinan, Shandong Province 250012, People's Republic of China.
authors.forename: Dujuan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Key Lab of Colloid and Interface Chemistry, Ministry of Education, Shandong University , Jinan, Shandong Province 250100, People's Republic of China.
authors.forename: Aixin
authors.initials: A
authors.lastname: Song
authors.affiliation: School of Pharmaceutical Science, Shandong University , 44 West Wenhua Road, Jinan, Shandong Province 250012, People's Republic of China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Luan
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008823:Micelles; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel