CaCO₃ Nanoparticles Delivering MicroRNA-200c Suppress Oral Squamous Cell Carcinoma

Area of Science:

• Biomedical Engineering
• Oncology
• Gene Therapy

Background:

• Oral squamous cell carcinoma (OSCC) is a prevalent head and neck cancer with high rates of recurrence, metastasis, and mortality.
• Current treatment outcomes for OSCC remain suboptimal, necessitating the development of novel therapeutic strategies.
• MicroRNA (miR)-200c has demonstrated tumor-suppressive properties, but its therapeutic application in OSCC via gene therapy has not been previously reported.

Purpose of the Study:

• To investigate the feasibility of using calcium carbonate (CaCO3)-based nanoparticles for nonviral delivery of plasmid DNA (pDNA) encoding miR-200c to inhibit OSCC growth.
• To evaluate the efficiency of CaCO3-based nanoparticles in transfecting OSCC cells with pDNA encoding miR-200c.
• To assess the impact of miR-200c overexpression on OSCC cell proliferation, migration, oncogene expression, and in vivo tumor growth.

Main Methods:

• CaCO3-based nanoparticles were formulated with varying ratios of CaCO3 and protamine sulfate (PS) to optimize pDNA miR-200c transfection efficiency in OSCC cells.
• The effects of miR-200c overexpression on OSCC cell proliferation and migration were quantified in vitro.
• In vivo tumor growth was evaluated using cell line-derived xenografts (CDX) in mice following local administration of CaCO3/pDNA miR-200c nanocomplexes.

Main Results:

• CaCO3-based nanoparticles demonstrated improved transfection efficiency for pDNA miR-200c, with the CaCO3 to PS ratio significantly influencing this process.
• Overexpression of miR-200c significantly suppressed OSCC cell proliferation, migration, and oncogene expression.
• Local administration of CaCO3/pDNA miR-200c nanocomplexes effectively inhibited tumor growth in a mouse CDX model.

Conclusions:

• The CaCO3/pDNA miR-200c nanocomplexes show significant potential as a nonviral gene delivery system for inhibiting OSCC progression.
• This novel approach may offer a promising strategy to reduce oral cancer recurrence and improve clinical outcomes.
• Further comprehensive preclinical studies are warranted to confirm the safety and efficacy of this CaCO3/pDNA miR-200c system across diverse models.