Delivery of miR-200c-3p Using Tumor-Targeted Mesoporous Silica Nanoparticles for Breast Cancer Therapy

Abstract

[EN] Despite advancesin breast cancer treatment, it remainsthe leadingcause of cancer-related death in women worldwide. In this context,microRNAs have emerged as potential therapeutic targets but stillpresent some limitations for in vivo applications.Particularly, miR-200c-3p is a well-known tumor suppressor microRNAthat inhibits tumor progression and metastasis in breast cancer throughdownregulating ZEB1 and ZEB2. Basedon the above, we describe the design and validation of a nanodeviceusing mesoporous silica nanoparticles for miR-200c-3p delivery forbreast cancer treatment. We demonstrate the biocompatibility of thesynthesized nanodevices as well as their ability to escape from endosomes/lysosomesand inhibit tumorigenesis, invasion, migration, and proliferationof tumor cells in vitro. Moreover, tumor targetingand effective delivery of miR-200c-3p from the nanoparticles in vivo are confirmed in an orthotopic breast cancer mousemodel, and the therapeutic efficacy is also evidenced by a decreasein tumor size and lung metastasis, while showing no signs of toxicity.Overall, our results provide evidence that miR-200c-3p-loaded nanoparticlesare a potential strategy for breast cancer therapy and a safe andeffective system for tumor-targeted delivery of microRNAs.