Co-Delivery of Repurposing Itraconazole and VEGF siRNA by Composite Nanoparticulate System for Collaborative Anti-Angiogenesis and Anti-Tumor Efficacy against Breast Cancer
Mingji Jin,
Bowen Zeng,
Yanhong Liu,
Lili Jin,
Yan Hou,
Chao Liu,
Wei Liu,
Hao Wu,
Liqing Chen,
Zhonggao Gao,
Wei Huang
Affiliations
Mingji Jin
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Bowen Zeng
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Yanhong Liu
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Lili Jin
Department of Pharmacy, Yanbian University, Yanji 133000, China
Yan Hou
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Chao Liu
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Wei Liu
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Hao Wu
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Liqing Chen
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Zhonggao Gao
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Wei Huang
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Combinations of two different therapeutic modalities of VEGF inhibitors against angiogenesis can cooperatively impede breast cancer tumor growth and enhance therapeutic efficacy. Itraconazole (ITZ) is a conventional antifungal drug with high safety; however, it has been repurposed to be a multi target anti-angiogenesis agent for cancer therapy in recent years. In the present study, composite nanoparticles co-loaded with ITZ and VEGF siRNA were prepared in order to investigate their anti-angiogenesis efficacy and synergistic anticancer effect against breast cancer. The nanoparticles had a suitable particle size (117.9 ± 10.3 nm) and weak positive surface charge (6.69 ± 2.46 mV), as well as good stability and drug release profile in vitro. Moreover, the nanoparticles successfully escaped from endosomes and realized cell apoptosis and cell proliferation inhibition in vitro. In vitro and in vivo experiments showed that the nanoparticles could induce the silencing of VEGF-related expressions as well as anti-angiogenesis efficacy, and the co-loaded ITZ-VEGF siRNA NPs could inhibit tumor growth effectively with low toxicity and side effects. Taken together, the as-prepared delivery vehicles are a simple and safe nano-platform that improves the antitumor efficacy of VEGF siRNA and ITZ, which allows the repositioning of the generic drug ITZ as a great candidate for antitumor therapy.
