Co-Delivery of Repurposing Itraconazole and VEGF siRNA by Composite Nanoparticulate System for Collaborative Anti-Angiogenesis and Anti-Tumor Efficacy against Breast Cancer

Abstract

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.

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820

“…As a drug delivery system, the efficiency of liposome internalization by target cells is crucial [ 19 ]. Cou-6, a fluorescent probe and laser dye, was used to track liposome uptake [ 20 ].…”

Recent Advances in Mesoporous Silica Nanoparticles Delivering siRNA for Cancer Treatment

“…Due to angiogenesis' pivotal function in the growth and propagation of tumors, VEGF has become a hot topic in antitumor angiogenesis research. Using VEGF siRNA to downregulate VEGF is a promising cancer treatment that inhibits tumor angiogenesis and metastasis [8]. Chen et al successfully inhibited the expression of the VEGF gene at the site of ovarian tumors by constructing M-MSN_siRNA@PEI-PEG-KALA loaded with VEGF siRNA [138].…”

“…The gene regulation of apoptosis-related proteins is an attainable antitumor approach to enhance drug-induced apoptosis and improve cytotoxicity. Moreover, overexpression of the Vascular Endothelial Growth Factor (VEGF) in tumor tissues drives angiogenesis and blocks the VEGF signaling pathway, which can be diminished by RNAi to prevent tumor growth [7,8]. siRNA-based gene therapy for the knocking down or downregulating immune checkpoint proteins (e.g., PD-L1 and STAT3), "don't eat me" signal (e.g., CD47), and anti-inflammatory cytokines (e.g., TGF-β) induces antitumor immune responses and significantly inhibits tumor growth in vivo [9][10][11][12].…”