CaCO₃Nanoparticles Delivering MicroRNA-200c Suppress Oral Squamous Cell Carcinoma

Abstract

MicroRNA (miR)-200c suppresses the initiation and progression of oral squamous cell carcinoma (OSCC), the most prevalent head and neck cancer with high recurrence, metastasis, and mortality rates. However,miR-200c-based gene therapy to inhibit OSCC growth and metastasis has yet to be reported. To develop an miR-based gene therapy to improve the outcomes of OSCC treatment, this study investigates the feasibility of plasmid DNA encodingmiR-200cdelivered via non-viral CaCO3-based nanoparticles to inhibit OSCC tumor growth. CaCO3-based nanoparticles with various ratios of CaCO3and protamine sulfate (PS) were utilized to transfect pDNA encodingmiR-200cinto OSCC cells and the efficiency of these nanoparticles was evaluated. The proliferation, migration, and associated oncogene production, as well asin vivotumor growth for OSCC cells overexpressingmiR-200cwere also quantified. It was observed that, while CaCO3-based nanoparticles improve transfection efficiencies of pDNAmiR-200c, the ratio of CaCO3to PS significantly influences the transfection efficiency. Overexpression ofmiR-200csignificantly reduced proliferation, migration, and oncogene expression of OSCC cells, as well as the tumor size of cell line-derived xenografts (CDX) in mice. In addition, a local administration of pDNAmiR-200cusing CaCO3delivery significantly enhancedmiR-200ctransfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO3/pDNAmiR-200cmay potentially be used to reduce oral cancer recurrence and metastasis and improve clinical outcomes in OSCC treatment. (227 words)