International Journal of Nanomedicine (Jun 2021)

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

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

Journal volume & issue
Vol. Volume 16
pp. 4001 – 4016

Abstract

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