Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang, 110001, China.
Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, China.
Adv Sci (Weinh). 2024 Feb;11(5):e2303907. doi: 10.1002/advs.202303907. Epub 2023 Nov 23.
Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte-leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.
尽管作为癌症治疗的一种有前途的新工具，肿瘤溶瘤病毒（OVs）的静脉内递送受到肿瘤靶向性差、血液中快速清除、严重的器官毒性和细胞因子释放综合征的极大限制。在此，报告了一种简单而有效的红细胞介导的溶瘤病毒治疗（ELeOVt）策略，该策略首次将 OVs 以接近 100%的效率组装在红细胞表面，并允许 OVs 在静脉注射后靶向递送至肺部，从而实现对肺转移的出色治疗，同时极大地提高了 OVs 作为药物的生物相容性。多聚亚乙基亚胺（PEI）作为将 OVs 组装在红细胞上的桥梁，也在促进 OVs 的转染中发挥了重要作用。研究发现，ELeOVt 方法显著延长了 OVs 的循环时间，并使 OVs 在肺部的分布增加了十倍以上，从而显著改善了肺转移的治疗效果，同时降低了器官和全身毒性。总之，这些发现表明，ELeOVt 为赋予 OVs 对抗肺转移的能力提供了一种生物相容性、高效且广泛可用的方法。
