Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland.
Nanomedicine. 2022 Feb;40:102506. doi: 10.1016/j.nano.2021.102506. Epub 2021 Dec 5.
Oncolytic viruses (OVs) selectively replicate in and destroy cancer cells resulting in anti-tumor immunity. However, clinical use remains a challenge because of virus clearance upon intravenous delivery. OV packaging using a nanomedicine approach could overcome this. Here we encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes in order to exploit recruitment of CCR2-expressing circulating monocytes into tumors. We demonstrate successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes that were preferentially taken up by CCR2-expressing monocytes. No complex-related toxicities were observed following incubation with prostate tumor cells and the encapsulation did not affect virus oncolytic activity in vitro. Furthermore, intravenous administration of our nanomedicine resulted in a significant reduction in tumor size and pulmonary metastasis in prostate cancer-bearing mice whereby a 1000-fold less virus was needed compared to Ad[I/PPT-E1A] alone. Taken together our data provide an opportunity to target OVs via circulation to inaccessible tumors using liposome-assisted drug delivery.
溶瘤病毒（OVs）选择性地在癌细胞中复制并破坏它们，从而产生抗肿瘤免疫。然而，由于静脉注射后病毒清除，其临床应用仍然是一个挑战。使用纳米医学方法对 OV 进行包装可以克服这一问题。在这里，我们将溶瘤腺病毒（Ad[I/PPT-E1A]）封装到 CCL2 包被的脂质体中，以利用表达 CCR2 的循环单核细胞募集到肿瘤中。我们证明了成功地将 Ad[I/PPT-E1A]封装到 CCL2 包被的脂质体中，这些脂质体优先被表达 CCR2 的单核细胞摄取。与前列腺肿瘤细胞孵育后没有观察到与复合物相关的毒性，并且封装不会影响病毒的体外溶瘤活性。此外，与单独使用 Ad[I/PPT-E1A]相比，静脉给予我们的纳米药物可显著减少前列腺癌荷瘤小鼠的肿瘤体积和肺转移，所需病毒量减少了 1000 倍。总之，我们的数据为通过使用脂质体辅助药物递送，通过循环将 OV 靶向到难以到达的肿瘤提供了机会。
