A pH/Ultrasound dual-response biomimetic nanoplatform for nitric oxide gas-sonodynamic combined therapy and repeated ultrasound for relieving hypoxia
A pH/Ultrasound dual-response biomimetic nanoplatform for nitric oxide gas-sonodynamic combined therapy and repeated ultrasound for relieving hypoxia
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pH/超声双重响应仿生纳米平台，用于一氧化氮气体声动力联合治疗和重复超声缓解缺氧
DOI：
10.1016/j.biomaterials.2019.119636
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发表时间：
2020-02-01
期刊：
影响因子：
14
通讯作者：
Zhao, Yuan-Di
中科院分区：
文献类型：
--
作者：
An, Jie;Hu, Yong-Guo;Zhao, Yuan-Di
声动力疗法（SDT）由于其内在的更深的组织穿透性而迅速发展成为传统光动力疗法的强大替代品。但由于肿瘤长期缺氧限制了其治疗效果，单次SDT治疗不能根治。为此，我们开发了一种具有双pH/超声响应、同源靶向和低光毒性的仿生纳米平台，用于一氧化氮（NO）气体与SDT联合治疗。该纳米平台是由沸石咪唑骨架-8材料包埋亚硝基谷胱甘肽（GSNO）和氯e6 （Ce6）一步包埋而成，然后用同源肿瘤细胞膜包裹。体外和体内实验表明，该仿生纳米平台具有良好的生物相容性，并通过同源靶向在肿瘤中具有较高的滞留性。重要的是，它可以在酸性肿瘤微环境中持续释放被包被的药物，并加速超声降解（US）。此外，GSNO释放的NO与US触发的Ce6产生的活性氧相互作用，生成高活性过氧亚硝酸盐，抑制肿瘤生长。此外，通过反复的US照射，可以长期缓解肿瘤缺氧，从而实现有效的气声动力联合治疗。本研究充分利用了US的优势，为高效肿瘤治疗提供了新的策略。
Sonodynamic therapy (SDT) has rapidly developed as a powerful alternative to traditional photodynamic therapy due to its intrinsically deeper tissue-penetration. However, single SDT dose is incapable of radical cure because the long-term hypoxia of tumor limits its therapeutic effect. Herein, we developed a biomimetic nanoplatform with dual pH/ultrasound response, homologous targeting and low phototoxicity for combined nitric oxide (NO) gas therapy with SDT to solve the problem. This nanoplatform is composed of zeolite imidazole framework-8 material embedded with nitrosoglutathione (GSNO) and chlorin e6 (Ce6) by one-step encapsulation, and then wrapped by homologous tumor cell membrane. In vitro and in vivo experiments indicate that the biomimetic nanoplatform has excellent biocompatibility and shows higher retention in tumor by homologous targeting. Importantly, it can sustainably release the encapsulated drug in acidic tumor microenvironment and accelerate degradation by ultrasound (US). Furthermore, NO released from GSNO and reactive oxygen species generated by Ce6, which are both triggered by US, react with each other to produce highly reactive peroxynitrite to inhibit the growth of tumor. Moreover, by repeated US irradiation, the tumor hypoxia can be relieved for a much-longer term, resulting in an effective gas-sonodynamic combined treatment. This study fully utilizes the advantages of US, providing a new strategy for high-performance cancer therapy.