title: Investigation of thermo-sensitive amphiphilic micelles as drug carriers for chemotherapy in cholangiocarcinoma in vitro and in vivo.
abstract: Cholangiocarcinoma is an epithelial cancer of the bile ducts with poor prognosis and, in recent years, a rapidly increasing incidence. In this study, nano-sized thermo-sensitive micelles were investigated as drug carriers to improve chemotherapy in cholangiocarcinoma. Thermo-sensitive amphiphilic block copolymer, P-(N,N-isopropylacrylamide-co-N-hydroxymethylacrylamide)-b-caprolactone [P-(NIPAAm-co-NHMAAm)-b-PCL] with lower critical solution temperature (LCST) at about 38°C was synthesized. Doxorubicin (DOX)-loaded micelles were prepared by dialysis method. The micelles exhibited a sustained and temperature-dependent DOX release. Toxicity of the blank micelles for human cholangiocarcinoma (QBC939) cells was minimal both in vitro and in vivo. In contrast, the DOX-loaded micelles effectively inhibited proliferation and induced apoptosis of QBC939 cells in vitro (p<0.05) and inhibited tumor growth in nude mice by 21.49%. These results indicated that thermo-sensitive amphiphilic micelles are a promising and effective drug carrier, and show potential for improving chemotherapy for cholangiocarcinoma.
authors.affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, PR China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, PR China.
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, PR China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, PR China. Electronic address: zhiwquan@yahoo.cn.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Quan
authors.affiliation: Institute of Nano and Bio-polymeric Materials, School of Material Science and Engineering, Tongji University, Cao An Road 4800, Shanghai 201804, PR China; Key Laboratory Advanced Civil Engineering Materials, Ministry of Education, School of Material Science and Engineering, Tongji University, Cao An Road 4800, Shanghai 201804, PR China. Electronic address: qgtan@tongji.edu.cn.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Tan
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D011091:Polyesters / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D004317:Doxorubicin; C067295:N-isopropylacrylamide; C066443:N-methylolacrylamide
keywords: Amphiphilic block copolymer; Cholangiocarcinoma; Drug carriers; Micelle; Thermo-sensitive