Tissue Engineering and Stem Cell Experiment Center, Guizhou Medical University (GMU), Guiyang, Guizhou, China; Department of Immunology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, China.
Department of Thoracic and Breast Surgery, Anshun People's Hospital, Anshun, Guizhou, China.
Virology. 2024 Oct;598:110196. doi: 10.1016/j.virol.2024.110196. Epub 2024 Jul 31.
Reovirus (Reo) has shown promising potential in specifically killing tumor cells, and offering new possibilities for ovarian cancer (OC) treatment. However, neutralizing antibodies in the ascites from OC patients greatly limit the further application of Reo. In this study, we employed cationic liposomes (Lipo) to deliver Reo, significantly enhancing its ability to enter OC cells and its effectiveness in killing these cells under ascitic conditions. Pre-treatment with the MβCD inhibitor notably decreased Reo-mediated tumor cell death, indicating that Lipo primarily enables Reo's cellular uptake through caveolin-mediated endocytosis. Our results demonstrate that Lipo effectively facilitates the entry of Reo into the cytoplasm and triggers cell apoptosis. The above findings provide a new strategy to overcome the obstacle of neutralizing antibodies in the clinical application of Reo.
呼肠孤病毒（Reo）在特异性杀伤肿瘤细胞方面显示出良好的应用前景，为卵巢癌（OC）的治疗提供了新的可能。然而，OC 患者腹水中的中和抗体极大地限制了 Reo 的进一步应用。在这项研究中，我们采用阳离子脂质体（Lipo）递送 Reo，显著提高了 Reo 进入 OC 细胞的能力，并增强了其在腹水条件下杀伤这些细胞的效果。MβCD 抑制剂的预处理显著降低了 Reo 介导的肿瘤细胞死亡，表明 Lipo 主要通过网格蛋白介导的内吞作用使 Reo 进入细胞。我们的结果表明，Lipo 能有效促进 Reo 进入细胞质并触发细胞凋亡。上述发现为克服 Reo 临床应用中中和抗体的障碍提供了一种新策略。
