期刊
BIOMATERIALS
卷 33, 期 27, 页码 6393-6407出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.05.052
关键词
Octreotide; Somatostatin receptors; Polymeric micelles; Chitosan; Tumor targeting
资金
- project of the National Natural Science Foundation of China [81102397]
- Innovative Project for Graduate Cultivation of Jiangsu Province [CXZZ11-0807]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKGQ201107]
- Specialized Research Fund for Doctoral Program of Higher Education of China [200803161017]
- Key New Drug Innovation Project from the Ministry of Science and Technology of China [2009ZX09310004]
- National Basic Research Program of China (973 Program) [2009CB903300]
In this study, a ligand-PEG-lipid conjugate, octreotide-polyethene glycol-deoxycholic acid (OCT(Phe)-PEG-DOCA, or OPD) was successfully synthesized and used as a targeting molecule for N-deoxycholic acid-O, N-hydroxyethylation chitosan (DAHC) micelles for efficient cancer therapy. DAHC micelles exhibited good loading capacities for doxorubicin (DOX), a model anti-cancer drug, and the modification of OPD showed no significant effect on drug load while slightly increasing the particle size and partly shielding the positive charges on the surface of micelles. Accelerated release rate of DOX from micelles were also observed after OPD modification and the release profile exhibited pH-sensitive properties. Compared with DAHC-DOX micelles, OPD-DAHC-DOX micelles exhibited significantly stronger cytotoxicity to MCF-7 cells (SSTRs overexpression) but with hardly any difference from WI-38 cells (no SSTRs expression). The results of flow cytometry and confocal laser scanning microscopy further revealed that OPD-DAHC-DOX micelles could be selectively taken into tumor cells by SSTRs-mediated endocytosis. In vivo investigation of micelles on nude mice bearing MCF-7 cancer xenografts confirmed that OPD-DAHC micelles possessed much higher tumor-targeting capacity than the DAHC control and exhibited enhanced anti-tumor efficacy and decreased systemic toxicity. These results suggest that OPD-DAHC micelles might be a promising anti-cancer drug delivery carrier for targeted cancer therapy. (c) 2012 Elsevier Ltd. All rights reserved.
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