CaCO3 Nanoparticles Delivering MicroRNA-200c Suppress Oral Squamous Cell Carcinoma
Q J Ding1, M T Remy1, C Upara1
1Iowa Institute for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, USA.
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 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 (pDNA) encoding miR-200c delivered via nonviral CaCO3-based nanoparticles to inhibit OSCC tumor growth. CaCO3-based nanoparticles with various ratios of CaCO3 and protamine sulfate (PS) were used to transfect pDNA encoding miR-200c into OSCC cells, and the efficiency of these nanoparticles was evaluated. The proliferation, migration, and associated oncogene production, as well as in vivo tumor growth for OSCC cells overexpressing miR-200c, were also quantified. It was observed that, while CaCO3-based nanoparticles improve transfection efficiencies of pDNA miR-200c, the ratio of CaCO3 to PS significantly influences the transfection efficiency. Overexpression of miR-200c significantly 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 pDNA miR-200c using CaCO3 delivery significantly enhanced miR-200c transfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO3/pDNA miR-200c may potentially be used to reduce oral cancer recurrence and improve clinical outcomes in OSCC treatment, while more comprehensive examinations to confirm the safety and efficacy of the CaCO3/pDNA miR-200c system using various preclinical models are needed.
Insights
This study developed a novel gene therapy using calcium carbonate nanoparticles to deliver microRNA-200c (miR-200c) for oral cancer treatment. The therapy effectively inhibited oral squamous cell carcinoma (OSCC) growth and migration in preclinical models.
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.
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