期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 492, 期 1-2, 页码 141-151出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2015.07.022
关键词
Chitosan; cRGDyK; Micelles; luc-A549; Orthotopic lung tumor
资金
- National Natural Science Foundation projects of China [81273463]
- Jiangsu Science and Technology Support Plan [BE2011670]
- Scientific Research Innovation projects of Graduate Students of Jiangsu Universities [CXLX13_840]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
This study aimed to prepare efficient cRGDyK peptide-decorated micelles for the targeted therapy of non-small-cell lung cancer (NSCLC). An amphiphilic copolymer N-succinyl-palmitoyl-chitosan (SPCS) was synthesized and characterized. cRGDyK peptide is a ligand that can target tumors via specific binding integrin receptor overexpressed on tumor neovascularization and cells. cRGDyK-functionalized SPCS micelles loaded with paclitaxel (PTX/cRGDyK-SPCS) were prepared by film dispersion method and then characterized according to morphology, size, and zeta potential. PTX/cRGDyK-SPCS micelles presented pH-triggered drug release behavior under acidic conditions. The accumulation of micelles detected by laser confocal fluorescence microscopy and flow cytometry showed that cRGDyK-SPCS micelles were easily taken up by A549 cells marked with the luciferase gene (luc-A549). Meanwhile, co-localization of the micelles and lysosomes was recorded dynamically using a live cell station. MTT assays and cell apoptosis studies revealed that cell viability was significantly inhibited by PTX/cRGDyK-SPCS micelles. More importantly, in vivo animal studies showed that cRGDyK-SPCS micelles mainly accumulated in the orthotopic tumor site. PTX/cRGDyK-SPCS micelles exhibited better anti-tumor activity in subcutaneous and orthotopic lung tumors compared with PTX/SPCS micelles and Taxol (R). These results suggested that PTX/cRGDyK-SPCS micelles had better cancer targeting capacity and superior anti-tumor efficacy. Thus, these micelles have great potential as novel carriers in delivering anti-tumor drugs. (C) 2015 Elsevier B.V. All rights reserved.
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