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Int. J. Mol. Sci. 2014, 15(12), 23571-23588; doi:10.3390/ijms151223571

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

1,2,3,†
,
4,†
,
1,2
,
4,* and 1,2,*
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
2
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China
3
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China
4
Surgical Department, the Affiliated Hospital of Yanbian University, Yanji 133000, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 12 September 2014 / Revised: 25 November 2014 / Accepted: 25 November 2014 / Published: 17 December 2014
(This article belongs to the Section Biomaterial Sciences)
View Full-Text   |   Download PDF [3705 KB, uploaded 17 December 2014]   |  

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. View Full-Text
Keywords: pancreatic ductal adenocarcinoma; small-sized polymeric micelles; docetaxel; permeability; orthotopic transplantation model pancreatic ductal adenocarcinoma; small-sized polymeric micelles; docetaxel; permeability; orthotopic transplantation model
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Li, Y.; Li, P.; Jin, M.; Jiang, C.; Gao, Z. Docetaxel-Encapsulating Small-Sized Polymeric Micelles with Higher Permeability and Its Efficacy on the Orthotopic Transplantation Model of Pancreatic Ductal Adenocarcinoma. Int. J. Mol. Sci. 2014, 15, 23571-23588.

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