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Journal of Chinese Pharmaceutical Sciences ›› 2015, Vol. 24 ›› Issue (8): 501-513.DOI: 10.5246/jcps.2015.08.064

• Original articles • Previous Articles     Next Articles

Vapreotide-modified nanomicelle as a targeted nanocarrier for delivering paclitaxel to the tumors with overexpression of somatostatin receptors

Wenjie Hou, Hua Zheng, Jiancheng Wang*   

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2015-05-03 Revised:2015-05-15 Online:2015-08-22 Published:2015-05-20
  • Contact: Tel.: 86-10-82805932; E-mail: wang-jc@bjmu.edu.cn
  • Supported by:

    National Basic Research Program of China (973 Program, Grant No. 2013CB932501), NSFC projects (Grant No. 81273455 and 81473158), and Programs from Ministry of Education (Grant No. NCET-11-0014 and BMU20110263).

Abstract:

Somatostatin receptors (SSTRs) were widely expressed in many tumor cells. As a somatostatin analogue, vapreotide (VAP) can be exploited as a modifier for targeting tumor therapy based on its high affinity to SSTR. In this study, we conjugated α-NH2 of exocyclic D-phenylalanine (D-Phe) of vapreotide to N-hydroxysuccinimidyl-PEG2000-DSPE (NHS-PEG-DSPE), and the resulted DSPE-PEG-VAP was used as a targeting component to construct the targeted micelles for delivering paclitaxel (VAP-M-PTX) through a thin-film hydration method. Similar particle size, zeta potential, drug encapsulation efficiencies, drug release behaviors and hemolysis effects were observed between the targeted micelles (VAP-M-PTX) and the non-targeted micelles (M-PTX). In MCF-7 cells, significantly higher intracellular fluorescence intensity (1.5-fold) was determined by flow cytometry after incubation of coumarin-6 loaded targeted micelles (VAP-M-Cou) for 3 h compared with non-targeted micelles (M-Cou), and similar finding was observed confocal microscopy. Furthermore, in comparison with non-targeted formulations, higher antitumorefficacy and higher drug accumulation were found in MCF-7 tumors in nude mice after intravenous injection of the targeted micelles. In conclusion, we believed that the vapreotide-modified nanomicelles could be a promising targeted nanocarrier for delivering anticancer drugs to the tumors with overexpression of somatostatin receptors.

Key words: Somatostatin receptor, Vapreotide, Targeted nanomicelle, Paclitaxel, Tumor therapy

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