Docetaxel-Encapsulating Small-Sized Polymeric Micelles with Higher Permeability and Its Efficacy on the Orthotopic Transplantation Model of Pancreatic Ductal Adenocarcinoma

International Journal of Molecular Sciences

Yunfei Li¹  Peiran Li²  Mingji Jin¹  Changgao Jiang²  Zhonggao Gao¹ 

[1] 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; E-Mails:;Surgical Department, the Affiliated Hospital of Yanbian University, Yanji 133000, China; E-Mail:

关键词: pancreatic ductal adenocarcinoma;    small-sized polymeric micelles;    docetaxel;    permeability;    orthotopic transplantation model;   

DOI  :  10.3390/ijms151223571

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.