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

Autores de IIS La Fe

• Félix Sancenón Galarza

  Autor

• Ramón Martínez Máñez

  Autor

• Pilar Eroles Asensio

  Autor

Participantes ajenos a IIS La Fe

• Garrido-Cano, Iris
• Adam-Artigues, Anna
• Lameirinhas, Ana
• Blandez, Juan F. F.
• Candela-Noguera, Vicente
• Lluch, Ana
• Bermejo, Begona
• Cejalvo, Juan Miguel

Grupos

• Unidad Mixta de Investigación en Nanomedicina y Sensores

Abstract

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.

Keywords

• breast cancer; mesoporous silica nanoparticles; microRNA; targeted delivery; therapy