title: Facile fabrication of redox-responsive thiol-containing drug delivery system via RAFT polymerization.
abstract: A novel kind of redox-responsive polymeric drug delivery system has been designed and prepared successfully through the coupling of the multithiol branched polymers and thiol-containing drugs. The branched poly((S-(4-vinyl) benzyl S'-propyltrithiocarbonate)-co-(poly(ethylene glycol) methacrylate)) (poly(VBPT-co-PEGMA)) was synthesized by one-pot reaction via reversible addition-fragmentation chain transfer (RAFT) copolymerization. Subsequently, the hydrophobic thiol-containing anticancer drug 6-mercaptopurine (MP) was conjugated to poly(VBPT-co-PEGMA) by thiol-disulfide exchange reaction, resulting in the formation of poly(VBPT-co-PEGMA)-S-S-MP conjugate. Due to its amphiphilicity, poly(VBPT-co-PEGMA)-S-S-MP conjugate self-assembled into amphiphilic micelles in aqueous solution. Under a reductive environment, the disassembly of polymeric micelles resulted in the MP release. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements demonstrated that the poly(VBPT-co-PEGMA)-S-S-MP micelles could be taken up by Raji cells (a Burkitt lymphoma cell line). The viability of the Raji cells incubated with the glutathione (GSH) mediated poly(VBPT-co-PEGMA)-S-S-MP micelles was investigated by Cell Counting Kit-8 (CCK-8) assay. The experimental results showed that the viability of the glutathione monoester (GSH-OEt) pretreated cells was lower than that without pretreatment, while the viability of the buthionine sulfoximine (BSO) pretreated cells was higher than that without pretreatment. The poly(VBPT-co-PEGMA)-S-S-MP micelles could induce the apoptosis of Raji cells, and the apoptosis behavior was dose-dependent. This redox-responsive polymer-drug conjugate provides a promising platform for the delivery of thiol-containing biological molecules.
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Yue
authors.initials: Y
authors.lastname: Su
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Dali
authors.initials: D
authors.lastname: Wang
authors.forename: Hongping
authors.initials: H
authors.lastname: Deng
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xi
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005434:Flow Cytometry; D005978:Glutathione; D057927:Hydrophobic and Hydrophilic Interactions; D015122:Mercaptopurine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008823:Micelles; D018613:Microscopy, Confocal; D015394:Molecular Structure; D041681:NIH 3T3 Cells / Q000187:drug effects; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D012996:Solutions; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008689:Methacrylates; D008823:Micelles; D012996:Solutions; D013438:Sulfhydryl Compounds; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; D019328:Buthionine Sulfoximine; D015122:Mercaptopurine; D005978:Glutathione