State Key Laboratory of Pharmaceutical Biotechnology, Medical School and School of Life Sciences, Nanjing University, Nanjing 210093, China.
National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China.
ACS Nano. 2021 Sep 28;15(9):15381-15394. doi: 10.1021/acsnano.1c07621. Epub 2021 Sep 14.
Hypoxia is one of the most important factors that limit the effect of radiotherapy, and the abundant HO in tumor tissues will also aggravate hypoxia-induced radiotherapy resistance. Delivering catalase to decompose HO into oxygen is an effective strategy to relieve tumor hypoxia and radiotherapy resistance. However, low stability limits catalase's application, which is one of the most common limitations for almost all proteins' internal utilization. Here, we develop catalase containing membrane vesicles (EMs) with excellent protease resistance to relieve tumor hypoxia for a long time. Even treated with 100-fold of protease, EMs showed higher catalase activity than free catalase. After being injected into tumors post 12 h, EMs maintained their hypoxia relief ability while free catalase lost its activity. Our results indicate that EMs might be an excellent catalase delivery for tumor hypoxia relief. Combined with their immune stimulation features, EMs could enhance radiotherapy and induce antitumor immune memory effectively.
缺氧是限制放疗效果的最重要因素之一，肿瘤组织中丰富的 HO 也会加剧缺氧诱导的放疗抵抗。将过氧化氢酶输送到组织中，将 HO 分解为氧气，是缓解肿瘤缺氧和放疗抵抗的有效策略。然而，低稳定性限制了过氧化氢酶的应用，这几乎是所有蛋白质内部利用的最常见限制之一。在这里，我们开发了含有过氧化氢酶的膜囊泡（EMs），具有优异的蛋白酶抗性，可以长时间缓解肿瘤缺氧。即使经过 100 倍的蛋白酶处理，EMs 显示出的过氧化氢酶活性仍高于游离过氧化氢酶。在注射到肿瘤后 12 小时，EMs 保持其缓解缺氧的能力，而游离过氧化氢酶失去活性。我们的结果表明，EMs 可能是一种缓解肿瘤缺氧的优秀过氧化氢酶输送载体。结合其免疫刺激特性，EMs 可以有效地增强放疗效果并诱导抗肿瘤免疫记忆。
