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GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar for improved in vivo anticolorectal cancer treatment

Authors Du Y, Zhang Q, Jing L, Liang X, Chi C, Li Y, Yang X, Dai Z, Tian J

Received 1 February 2015

Accepted for publication 30 March 2015

Published 28 May 2015 Volume 2015:10(1) Pages 3791—3802

DOI https://doi.org/10.2147/IJN.S82029

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Yang Du,1,* Qian Zhang,1,* Lijia Jing,2 Xiaolong Liang,2 Chongwei Chi,1 Yaqian Li,1 Xin Yang,1 Zhifei Dai,2 Jie Tian1

1Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Biomedical Engineering, College of Engineering, Peking University, Beijing People’s Republic of China

*These authors contributed equally to this work

Abstract: Tumor angiogenesis plays a key role in tumor growth and metastasis; thus, targeting tumor-associated angiogenesis is an important goal in cancer therapy. However, the efficient delivery of drugs to tumors remains a key issue in antiangiogenesis therapy. GX1, a peptide identified by phage-display technology, is a novel tumor vasculature endothelium-specific ligand and possesses great potential as a targeted vector and antiangiogenic agent in the diagnosis and treatment of human cancers. Endostar, a novel recombinant human endostatin, has been shown to inhibit tumor angiogenesis. In this study, we developed a theranostic agent composed of GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar (GPENs) and labeled with the near-infrared dye IRDye 800CW to improve colorectal tumor targeting and treatment efficacy in vivo. The in vivo fluorescence molecular imaging data showed that GPENs (IRDye 800CW) more specifically targeted tumors than free IRDye 800CW in colorectal tumor-bearing mice. Moreover, the antitumor efficacy was evaluated by bioluminescence imaging and immunohistology, revealing that GPENs possessed improved antitumor efficacy on subcutaneous colorectal xenografts compared to other treatment groups. Thus, our study showed that GPENs, a novel GX1 peptide guided form of nanoscale Endostar, can be used as a theranostic agent to facilitate more efficient targeted therapy and enable real-time monitoring of therapeutic efficacy in vivo.

Keywords: GX1 peptide, Endostar, colorectal cancer, angiogenesis, IRDye 800CW, molecular imaging

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