title: Docetaxel-encapsulating small-sized polymeric micelles with higher permeability and its efficacy on the orthotopic transplantation model of pancreatic ductal adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance, and the small-sized nanocarrier loaded with platinum has been adopted to address this problem which is not suitable for loading docetaxel (DTX). In the present study, we used the poly(D,L-lactide)-b-polyethylene glycol-methoxy (mPEG-b-PDLLA) to encapsulate DTX and got a small-sized polymeric micelle (SPM); meanwhile we functionalized the SPM's surface with TAT peptide (TAT-PM) for a higher permeability. The diameters of both SPM and TAT-PM were in the range of 15-26 nm. In vitro experiments demonstrated that TAT-PM inhibited Capan-2 Luc PDAC cells growth more efficiently and induced more apoptosis compared to SPM and Duopafei. The in vivo therapeutic efficiencies of SPM and TAT-PM compared to free DTX was investigated on the orthotopic transplantation model of Capan-2 Luc. SPM exerted better therapeutic efficiency than free DTX, however, TAT-PM didn't outperformed SPM. Overall, these results disclosed that SPM could represent a new therapeutic approach against pancreatic cancer, but its permeability to PDAC was not the only decisive factor.
authors.affiliation: State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. mail_liyunfei@163.com.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Surgical Department, the Affiliated Hospital of Yanbian University, Yanji 133000, China. lipeiran_2009@163.com.
authors.forename: Peiran
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. jinmingji@imm.ac.cn.
authors.forename: Mingji
authors.initials: M
authors.lastname: Jin
authors.affiliation: Surgical Department, the Affiliated Hospital of Yanbian University, Yanji 133000, China. chjiang@ybu.edu.cn.
authors.forename: Changgao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. zggao@imm.ac.cn.
authors.forename: Zhonggao
authors.initials: Z
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005260:Female; D006801:Humans; D051379:Mice; D008823:Micelles; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel