Iowa Institute for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, USA.
Department of Chemistry, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, USA.
J Dent Res. 2024 Feb;103(2):147-155. doi: 10.1177/00220345231216110. Epub 2023 Dec 27.
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, -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 delivered via nonviral CaCO-based nanoparticles to inhibit OSCC tumor growth. CaCO-based nanoparticles with various ratios of CaCO and protamine sulfate (PS) were used to transfect pDNA encoding 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 , were also quantified. It was observed that, while CaCO-based nanoparticles improve transfection efficiencies of pDNA , the ratio of CaCO to PS significantly influences the transfection efficiency. Overexpression of 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 using CaCO delivery significantly enhanced transfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO/pDNA 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 CaCO/pDNA system using various preclinical models are needed.
微小 RNA（miR）-200c 抑制口腔鳞状细胞癌（OSCC）的发生和发展，OSCC 是最常见的头颈部癌症，其复发率、转移率和死亡率都很高。然而，基于 的基因治疗抑制 OSCC 生长尚未见报道。为了开发基于 miR 的基因治疗方法来改善 OSCC 治疗的效果，本研究探讨了通过非病毒 CaCO 基纳米粒子转染编码 的质粒 DNA（pDNA）抑制 OSCC 肿瘤生长的可行性。使用不同 CaCO 和鱼精蛋白硫酸盐（PS）比例的 CaCO 基纳米粒子转染编码 的 pDNA，并评估这些纳米粒子的效率。还定量分析了过表达 的 OSCC 细胞的增殖、迁移和相关致癌基因的产生，以及体内肿瘤生长情况。结果表明，CaCO 基纳米粒子虽然可以提高 pDNA 的转染效率，但 CaCO 与 PS 的比例对转染效率有显著影响。过表达 显著降低了 OSCC 细胞的增殖、迁移和致癌基因表达，以及小鼠来源的细胞系异种移植（CDX）的肿瘤大小。此外，使用 CaCO 递送系统局部给予 pDNA 显著增强了 CDX 中 的转染并抑制了肿瘤生长。这些结果强烈表明，CaCO/pDNA 纳米复合物可能有潜力用于减少口腔癌复发，并改善 OSCC 治疗的临床效果，同时需要使用各种临床前模型更全面地检查 CaCO/pDNA 系统的安全性和有效性。
