Synthesis and Antitumor Activity of Targeting and Nano Drug-Carrying Micelles Mediated by Rabies-virus-derived Peptide RVG29

doi:10.7503/cjcu20150941

Chem. J. Chinese Universities ›› 2016, Vol. 37 ›› Issue (4): 661.doi: 10.7503/cjcu20150941

• Organic Chemistry • Previous Articles Next Articles

Synthesis and Antitumor Activity of Targeting and Nano Drug-Carrying Micelles Mediated by Rabies-virus-derived Peptide RVG29

HAN Hailing^1,2, JIN Shunzi¹, MIAO Zhuang³, CHEN Ping³, WANG Zhanfeng³, XIE Zhigang⁴

1. Ministry of Health Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China;
2. Department of Cardiac, Affiliated Hospital of Beihua University, Jilin 132011, China;
3. Department of Neurosurgery, China Japan Union Hospital, Jilin University, Changchun 130033, China;
4. State Key Lab of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Changchun 130022, China

Received:2015-12-09 Online:2016-04-10 Published:2016-03-04
Supported by:
Supported by the National Natural Science Foundation of China(No.20904002), the Program for New Century Excellent Talents in University of Ministry of Education of China(No.NCET-10-0171), the Young Scholars Programs of Science and Technology Commission Foundation of Jilin Province, China(No. 20130522020JH), the Programs of Educational Commission of Jilin Province of China During the 12th Five-Year Plan Period(No.2013107027) and the High-Technology Research and Development Programs of Jilin Province of China(No.JF2012C005-2).

Abstract

Abstract:

Starting with water soluble dextran(Dex), paclitaxel(PTX)-carrying micelles M(PTX) and Rabies-virus-derived peptide(RVG29)-targeted and PTX-carrying micelles M(RVG,PTX) were prepared, by carboxylation of dextran and subsequently by conjugating PTX and RVG29 onto the carboxylated dextran. The products were characterized with nuclear magnetic resonance(¹H NMR) spectroscopy, transmission electron microscopy(TEM), and dynamic light scattering(DLS). The uptakes of the micelles by C₆ cells and the inhibition rates of C₆ cell growth by the micelles were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay, by confocal laser scanning microscopy(CLSM), and by flow cytometry(FCM). The results showed that molecular weight of Dex-PTX was about 16500 and that of RVG-Dex-PTX was about 19800. Micelles M(PTX) and M(RVG, PTX) assumed a shape of spheres with a diameter of 45-60 nm. The mass ratio of Dex, PTX and RVG29 was about 100: 20: 10. M(RVG, PTX) exhibited higher cell growth inhibition rate against C₆ cells than M(PTX) and C₆ cells took in more M(RVG,PTX) than M(PTX) under the same experimental conditions. When C₆ cells were treated with free RVG29 prior to cellular experiments, the inhibition rate against C₆ cells and the uptake by C₆ cells of M(RVG,PTX) were significantly decreased and came to a level of M(PTX). This implied that the enhanced inhibition of C₆ cell growth by M(RVG,PTX) and the enhanced uptake of M(RVG,PTX) by C₆ cells were mediated by RVG29, and the RVG29 species after conjugation with Dex reserved the targeting ability of RVG29 itself to a reasonable extent. Furthermore, in the preparation of M(RVG, PTX) micelles, only Dex was used as a carrier polymer, no hydrophobic polymer segments were involvd and there was no need of preparing drug-carrying copolymers and targeting copolymers, separately, and then doing co-assembling of them. In short, the manufacturing of M(RVG,PTX) micelles is relatively simple but they have the functions of drug-carrying and C₆-cell targeting, therefore, their practical application is expected.

Key words: Rabies-virus-derived peptide, Glioma, Tumor targeting, Paclitaxel, Nano drug-carrying micelle

CLC Number:

O629
R730

TrendMD:

HAN Hailing, JIN Shunzi, MIAO Zhuang, CHEN Ping, WANG Zhanfeng, XIE Zhigang. Synthesis and Antitumor Activity of Targeting and Nano Drug-Carrying Micelles Mediated by Rabies-virus-derived Peptide RVG29[J]. Chem. J. Chinese Universities, 2016, 37(4): 661.

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Synthesis and Antitumor Activity of Targeting and Nano Drug-Carrying Micelles Mediated by Rabies-virus-derived Peptide RVG29

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