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Specific targeting of A54 homing peptide-functionalized dextran-g-poly(lactic-co-glycolic acid) micelles to tumor cells

Authors Situ JQ, Ye YQ, Zhu XL, Yu RS, You J, Yuan H, Hu FQ, Du YZ

Received 23 October 2014

Accepted for publication 1 December 2014

Published 17 January 2015 Volume 2015:10(1) Pages 665—675

DOI https://doi.org/10.2147/IJN.S76307

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Jun-Qing Situ,1 Yi-Qing Ye,2 Xiu-Liang Zhu,3 Ri-Sheng Yu,3 Jian You,1 Hong Yuan,1 Fu-Qiang Hu,1 Yong-Zhong Du1

1College of Pharmaceutical Sciences, 2Women’s Hospital, 3Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China

Abstract: The delivery of chemotherapeutics into tumor cells is a fundamental knot for tumor-target therapy to improve the curative effect and avoid side effects. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA self-assembled to form micelles with a low critical micelle concentration of 16.79 µg·mL-1 and diameter of about 50 nm. With doxorubicin (DOX) base as a model antitumor drug, the drug-encapsulation efficiency of DOX-loaded A54-Dex-PLGA micelles (A54-Dex-PLGA/DOX) reached up to 75%. In vitro DOX release from the A54-Dex-PLGA/DOX was prolonged to 72 hours. The A54-Dex-PLGA micelles presented excellent internalization ability into hepatoma cells (BEL-7402 cell line and HepG2 cell line) in vitro, and the cellular uptake of the micelles by the BEL-7402 cell line was specific, which was demonstrated by the blocking experiment. In vitro antitumor activity studies confirmed that A54-Dex-PLGA/DOX micelles suppressed tumor-cell (BEL-7402 cell) growth more effectively than Dex-PLGA micelles. Furthermore, in vivo biodistribution testing demonstrated that the A54-Dex-PLGA micelles had a higher distribution ability to BEL-7402 tumors than that to HepG2 tumors.

Keywords: homing peptide, polymeric micelles, doxorubicin, tumor-cell targeting

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