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Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis

Authors Wang F, Li Y, Jiang H , Li C, Li Z, Qi C, Li Z , Gao Z, Zhang B, Wu J 

Received 5 March 2021

Accepted for publication 17 May 2021

Published 9 June 2021 Volume 2021:16 Pages 4001—4016


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Phong A Tran

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Fangqing Wang, 1,* Yanying Li, 1,* Hong Jiang, 1,* Chenglei Li, 2 Zhaohuan Li, 2 Cuiping Qi, 3 Zhipeng Li, 1 Zhiqin Gao, 1 Bo Zhang, 2 Jingliang Wu 1

1School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China; 2School of Pharmacy, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3School of Nursing, Weifang Medical University, Weifang, 261053, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Bo Zhang; Jingliang Wu Email [email protected] ; [email protected]

Background: Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy.
Methods: Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel “BEL-7402+HUVEC” co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test.
Results: The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery.
Conclusion: CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.

Keywords: dual-ligand-modified, liposomes, anti-angiogenesis, VEGF, co-delivery

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