胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，迫切需要有效的治疗。溶瘤腺病毒（OA）有望成为临床抗肿瘤治疗的潜在候选者，包括治疗 GBM。然而，OA 的全身给药仍然面临挑战，导致抗肿瘤功效显着受损。在本研究中，我们开发了一种创新方法，通过用单宁酸和Fe3（TA-Fe3）封装CXCL11-armed OA来实现OA的全身递送。在体外和体内评估了纳米载体保护 OA 免遭宿主免疫反应消除的能力。我们评估了 OA@TA-Fe3 在 GBM 小鼠模型中的抗肿瘤作用和安全性。 OA@TA-Fe3有效保护病毒免受宿主免疫清除并延长其在体内的循环。靶向肿瘤部位后，TA-Fe3 可以溶解并释放 Fe3 和 OA。 Fe3诱导H2O2产生O2缓解缺氧状态，促进OA复制，从而显着改变肿瘤免疫微环境并增强抗肿瘤功效。此外，OA@TA-Fe3 的全身递送是安全的，没有炎症或器官损伤。我们的研究结果证明了系统地提供工程化 OA 来有效治疗 GBM 的溶瘤病毒疗法的巨大潜力。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

Glioblastoma (GBM) represents the most aggressive primary brain tumor, and urgently requires effective treatments. Oncolytic adenovirus (OA) shows promise as a potential candidate for clinical antitumor therapy, including in the treatment of GBM. Nevertheless, the systemic delivery of OA continues to face challenges, leading to significantly compromised antitumor efficacy. In this study, we developed an innovative approach by encapsulating CXCL11-armed OA with tannic acid and Fe3+ (TA-Fe3+) to realize the systemic delivery of OA. The nanocarrier's ability to protect the OA from elimination by host immune response was evaluated in vitro and in vivo. We evaluated the antitumor effect and safety profile of OA@TA-Fe3+ in a GBM-bearing mice model. OA@TA-Fe3+ effectively safeguarded the virus from host immune clearance and extended its circulation in vivo. After targeting tumor sites, TA-Fe3+ could dissolve and release Fe3+ and OA. Fe3+-induced O2 production from H2O2 relieved the hypoxic state, and promoted OA replication, leading to a remarkable alteration of tumor immune microenvironment and enhancement in antitumor efficacy. Moreover, the systemic delivery of OA@TA-Fe3+ was safe without inflammation or organ damage. Our findings demonstrated the promising potential of systemically delivering the engineered OA for effective oncolytic virotherapy against GBM.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.