Ding Qiong J, Remy Matthew T, Upara Chawin, Hu Jue, Mata Andrés V Mora, Haes Amanda J, Lanzel Emily, Sun Hongli, Buchakjian Marisa R, Hong Liu
bioRxiv. 2023 Oct 5:2023.10.05.561110. doi: 10.1101/2023.10.05.561110.
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 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 encoding delivered via non-viral CaCO -based nanoparticles to inhibit OSCC tumor growth. CaCO -based nanoparticles with various ratios of CaCO and protamine sulfate (PS) were utilized 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 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 metastasis and improve clinical outcomes in OSCC treatment. (227 words).
微小RNA(miR)-200c可抑制口腔鳞状细胞癌(OSCC)的发生和发展,OSCC是最常见的头颈癌,具有高复发率、高转移率和高死亡率。然而,基于miR的抑制OSCC生长和转移的基因治疗尚未见报道。为了开发基于miR的基因治疗以改善OSCC的治疗效果,本研究调查了通过非病毒碳酸钙基纳米颗粒递送编码miR-200c的质粒DNA来抑制OSCC肿瘤生长的可行性。利用具有不同碳酸钙(CaCO₃)与硫酸鱼精蛋白(PS)比例的碳酸钙基纳米颗粒将编码miR-200c的质粒DNA转染到OSCC细胞中,并评估这些纳米颗粒的效率。还对过表达miR-200c的OSCC细胞的增殖、迁移、相关癌基因产生以及肿瘤生长进行了定量分析。结果发现,虽然碳酸钙基纳米颗粒可提高质粒DNA-miR-200c的转染效率,但CaCO₃与PS的比例对转染效率有显著影响。miR-200c的过表达显著降低了OSCC细胞的增殖、迁移和癌基因表达,以及小鼠体内细胞系来源异种移植物(CDX)的肿瘤大小。此外,使用碳酸钙递送系统局部给予质粒DNA-miR-200c可显著增强转染效果并抑制小鼠体内CDX的肿瘤生长。这些结果有力地表明,CaCO₃/质粒DNA-miR-200c纳米复合物可能可用于降低口腔癌的复发和转移,并改善OSCC治疗的临床效果。 (227字)