尽管最近的医学进展，宫颈癌仍然是全球女性的主要健康问题。目前的标准治疗方法存在非特异性毒性等局限性，因此需要开发更安全、更有效的治疗策略。这项研究评估了富含抗癌多酚的橄榄叶提取物 (OLE) 和溶瘤新城疫病毒 (NDV) 对人类宫颈癌细胞的组合作用。 OLE 被有效封装（>94% 负载）在 MF59 脂质纳米粒子和纳米结构脂质载体（NLC；包含 Precirol 作为 NLC-P，包含卵磷脂作为 NLC-L）中，以增强稳定性、生物利用度和靶向递送。物理化学分析证实 OLE 成功封装在小于 150 nm 的纳米颗粒内。体外细胞毒性测定表明，与 HDF 正常细胞相比，负载 OLE 的纳米颗粒制剂对 HeLa 癌细胞的毒性显着更高（P<0.05）。 MF59 实现了最高的包封率，而 NLC-P 具有最佳的药物释放曲线。与 HDF 细胞相比，NDV 选择性感染并杀死 HeLa 细胞。值得注意的是，将NDV与负载OLE的纳米粒子结合可显着增强对癌细胞的协同细胞毒性（P<0.05），其中NLC-P（OLE）和NDV产生最强的效果。细胞凋亡和细胞周期分析证实了组合治疗的抗癌活性增加，从而诱导细胞周期停滞。这项研究提供的证据表明，共同递送 OLE 负载的脂质纳米颗粒和 NDV 通过协同机制在体外增强对宫颈癌细胞的抗癌活性，从而保证了作为一种有前途的替代宫颈癌疗法的进一步发展。版权所有：© 2024 Golalipour 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Despite recent medical progress, cervical cancer remains a major global health concern for women. Current standard treatments have limitations such as non-specific toxicity that necessitate development of safer and more effective therapeutic strategies. This research evaluated the combinatorial effects of olive leaf extract (OLE), rich in anti-cancer polyphenols, and the oncolytic Newcastle disease virus (NDV) against human cervical cancer cells. OLE was efficiently encapsulated (>94% loading) within MF59 lipid nanoparticles and nanostructured lipid carriers (NLCs; contains Precirol as NLC-P, contains Lecithin as NLC-L) to enhance stability, bioavailability, and targeted delivery. Physicochemical analysis confirmed successful encapsulation of OLE within nanoparticles smaller than 150 nm. In vitro cytotoxicity assays demonstrated significantly higher toxicity of the OLE-loaded nanoparticle formulations on HeLa cancer cells versus HDF normal cells (P<0.05). MF59 achieved the highest encapsulation efficiency, while NLC-P had the best drug release profile. NDV selectively infected and killed HeLa cells versus HDF cells. Notably, combining NDV with OLE-loaded nanoparticles led to significantly enhanced synergistic cytotoxicity against cancer cells (P<0.05), with NLC-P (OLE) and NDV producing the strongest effects. Apoptosis and cell cycle analyses confirmed the increased anti-cancer activity of the combinatorial treatment, which induced cell cycle arrest. This study provides evidence that co-delivery of OLE-loaded lipid nanoparticles and NDV potentiates anti-cancer activity against cervical cancer cells in vitro through a synergistic mechanism, warranting further development as a promising alternative cervical cancer therapy.Copyright: © 2024 Golalipour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.