Liang Yujia, Cai Zhengmin, Tang Yamei, Su Chenglin, Xie Liye, Li Yan, Liang Xinqiang
Guangxi Medical University Cancer Hospital, Nanning, China.
Front Bioeng Biotechnol. 2023 May 24;11:1196839. doi: 10.3389/fbioe.2023.1196839. eCollection 2023.
Reactive oxygen species (ROS)-mediated therapies have typically been considered as noninvasive tumor treatments owing to their high selectivity and efficiency. However, the harsh tumor microenvironment severely impairs their efficiency. Herein, the biodegradable Cu-doped zeolitic imidazolate framework-8 (ZIF-8) was synthesized for loading photosensitizer Chlorin e6 (Ce6) and CaO nanoparticles, followed by surface decoration by hyaluronic acid (HA), obtaining HA/CaO-Ce6@Cu-ZIF nano platform. Once HA/CaO-Ce6@Cu-ZIF targets tumor sites, the degradation of Ce6 and CaO release from the HA/CaO-Ce6@Cu-ZIF in response to the acid environment, while the Cu active sites on Cu-ZIF are exposed. The released CaO decompose to generate hydrogen peroxide (HO) and oxygen (O), which alleviate the insufficiency of intracellular HO and hypoxia in tumor microenvironment (TME), effectively enhancing the production of hydroxyl radical (•OH) and singlet oxygen (O) in Cu-mediated chemodynamic therapy (CDT) and Ce6-induced photodynamic therapy (PDT), respectively. Importantly, Ca originating from CaO could further enhance oxidative stress and result in mitochondrial dysfunction induced by Ca overloading. Thus, the HO/O self-supplying and Ca overloading ZIF-based nanoplatform for cascade-amplified CDT/PDT synergistic strategy is promising for highly efficient anticancer therapy.
活性氧（ROS）介导的疗法因其高选择性和高效性，通常被视为非侵入性肿瘤治疗方法。然而，恶劣的肿瘤微环境严重削弱了它们的疗效。在此，合成了可生物降解的铜掺杂沸石咪唑酯骨架-8（ZIF-8），用于负载光敏剂二氢卟吩e6（Ce6）和氧化钙纳米颗粒，随后用透明质酸（HA）进行表面修饰，得到HA/CaO-Ce6@Cu-ZIF纳米平台。一旦HA/CaO-Ce6@Cu-ZIF靶向肿瘤部位，Ce6降解，CaO在酸性环境中从HA/CaO-Ce6@Cu-ZIF中释放出来，同时Cu-ZIF上的铜活性位点暴露。释放出的CaO分解产生过氧化氢（HO）和氧气（O），这缓解了肿瘤微环境（TME）中细胞内HO的不足和缺氧状况，分别有效增强了铜介导的化学动力学疗法（CDT）中羟基自由基（•OH）和光动力疗法（PDT）中Ce6诱导产生的单线态氧（O）的生成。重要的是，源自CaO的Ca2+可进一步增强氧化应激，并导致Ca2+过载诱导的线粒体功能障碍。因此，基于ZIF的HO/O自供应和Ca2+过载纳米平台用于级联放大的CDT/PDT协同策略，在高效抗癌治疗方面具有广阔前景。
