期刊
PHARMACEUTICS
卷 14, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14071369
关键词
itraconazole; VEGF siRNA; siRNA delivery; breast cancer; co-inhibition
资金
- National Natural Science Fund of China [82104106, 82073778]
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2021-I2M-1-026]
The co-delivery of Itraconazole (ITZ) and VEGF siRNA using composite nanoparticles was shown to effectively inhibit angiogenesis and tumor growth in breast cancer, with low toxicity and side effects.
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.
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