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

• DOI: 10.1021/acsami.3c07541
• Publication Date: 2023-08-07T20:45:06Z
• Authors: Iris Garrido-Cano; Anna Adam-Artigues; Ana Lameirinhas; Juan F. Blandez; Vicente Candela-N...; Ana Lluch; Begoña Bermejo; Felix Sancenón; Juan Miguel Cejalvo; Ramón Martínez-Máñez; Pilar Eroles
• Keywords: therapy; Lung Neoplasms; microRNA; Mesoporous silica nanoparticles; QUIMICA INORGANICA; targeted delivery; MicroRNA; Silicon Dioxide; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; MicroRNAs; breast cancer; Breast cancer; QUIMICA ORGANICA; Cell Movement; Cell Line, Tumor; breast cancer, mesoporous silica nanoparticles, microRNA, targeted delivery, therapy; Animals; Nanoparticles; Female; Therapy; Targeted delivery; mesoporous silica nanoparticles; Cell Proliferation

Despite advances in breast cancer treatment, it remains the leading cause of cancer-related death in women worldwide. In this context, microRNAs have emerged as potential therapeutic targets but still present some limitations for in vivo applications. Particularly, miR-200c-3p is a well-known tumor suppressor microRNA that inhibits tumor progression and metastasis in breast cancer through downregulating ZEB1 and ZEB2. Based on the above, we describe the design and validation of a nanodevice using mesoporous silica nanoparticles for miR-200c-3p delivery for breast cancer treatment. We demonstrate the biocompatibility of the synthesized nanodevices as well as their ability to escape from endosomes/lysosomes and inhibit tumorigenesis, invasion, migration, and proliferation of tumor cells in vitro. Moreover, tumor targeting and effective delivery of miR-200c-3p from the nanoparticles in vivo are confirmed in an orthotopic breast cancer mouse model, and the therapeutic efficacy is also evidenced by a decrease in tumor size and lung metastasis, while showing no signs of toxicity. Overall, our results provide evidence that miR-200c-3p-loaded nanoparticles are a potential strategy for breast cancer therapy and a safe and effective system for tumor-targeted delivery of microRNAs.