Sánchez-Meza Luz Victoria, Bello-Rios Ciresthel, Eloy Josimar O, Gómez-Gómez Yazmín, Leyva-Vázquez Marco Antonio, Petrilli Raquel, Bernad-Bernad María Josefa, Lagunas-Martínez Alfredo, Medina Luis Alberto, Serrano-Bello Janeth, Organista-Nava Jorge, Illades-Aguiar Berenice
Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Chilpancingo 39090, Guerrero, Mexico.
Department of Pharmacy, Dentistry and Nursing, Faculty of Pharmacy, Federal University of Ceará, 1210 Pastor Samuel Munguba Street, Fortaleza 60430-160, CE, Brazil.
Pharmaceutics. 2024 Jun 29;16(7):880. doi: 10.3390/pharmaceutics16070880.
The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.
高危型人乳头瘤病毒（HR-HPV）的E6和E7癌蛋白对宫颈癌（CC）的发展至关重要。小干扰RNA（siRNAs）作为使这些癌基因沉默的新型疗法正在被探索，但它们的临床应用受到低效递送系统的阻碍。用聚乙二醇（PEG）对脂质体siRNA复合物（siRNA脂质复合物）进行修饰（聚乙二醇化）可能会提高其全身稳定性。我们研究了通过阳离子脂质体（脂质复合物）递送的靶向HPV16 E6的siRNA对宫颈癌细胞系（CaSki）细胞过程的影响及其潜在的治疗用途。制备了由DOTAP、胆固醇、二油酰磷脂酰乙醇胺（DOPE）和二硬脂酰磷脂酰乙醇胺-聚乙二醇2000（DSPE-PEG2000）组成的脂质复合物-PEG-HPV16 E6。结果表明，聚乙二醇化（5% DSPE-PEG2000）提供了稳定的siRNA保护，粒径为86.42±3.19 nm，复合效率超过80%；siRNA在30天内保持稳定。这些脂质复合物显著降低了HPV16 E6蛋白水平并恢复了p53蛋白表达，分别在20 nM、200 nM和80 nM的浓度下抑制了致癌过程，如增殖25.74%、迁移（95.7%）和细胞侵袭（97.8%）。总之，阳离子脂质复合物-PEG-HPV16 E6作为在宫颈癌中沉默HPV16 E6的siRNA载体显示出前景。
