title: Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.
abstract: 7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles.
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, & Institutes of Biomedical Science, Fudan University, Shanghai 200040, China; Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, & Institutes of Biomedical Science, Fudan University, Shanghai 200040, China; Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Digestion, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, & Institutes of Biomedical Science, Fudan University, Shanghai 200040, China; Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, & Institutes of Biomedical Science, Fudan University, Shanghai 200040, China; Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Hangzhou PushKang Biotechnology Co., Ltd., Zhejiang, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Hangzhou PushKang Biotechnology Co., Ltd., Zhejiang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, & Institutes of Biomedical Science, Fudan University, Shanghai 200040, China; Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China. Electronic address: jiahuliang@huashan.org.cn.
authors.forename: Huliang
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, & Institutes of Biomedical Science, Fudan University, Shanghai 200040, China; Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China. Electronic address: qin_lx@yahoo.com.
authors.forename: Lunxiu
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers; D065546:Drug Liberation; D005260:Female; D045325:HCT116 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D007279:Injections, Subcutaneous; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013329:Structure-Activity Relationship; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin
keywords: Block co-polymers; Cancer; Micelles; Regression; SN38