Biodegradable Biomimic Copper/Manganese Silicate Nanospheres for Chemodynamic/Photodynamic Synergistic Therapy with Simultaneous Glutathione Depletion and Hypoxia Relief
Biodegradable Biomimic Copper/Manganese Silicate Nanospheres for Chemodynamic/Photodynamic Synergistic Therapy with Simultaneous Glutathione Depletion and Hypoxia Relief
复制标题
可生物降解的仿生铜/硅酸锰纳米球，用于同时消耗谷胱甘肽和缓解缺氧的化学动力学/光动力学协同疗法
DOI：
10.1021/acsnano.8b09387
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发表时间：
2019-04-01
期刊：
影响因子：
17.1
通讯作者：
Zhang, Xueji
中科院分区：
文献类型：
--
作者：
Liu, Conghui;Wang, Dongdong;Zhang, Xueji
活性氧（ROS）参与的光动力疗法（PDT）和化学动力疗法（CDT）的整合对于增强抗癌效果具有很大的希望。在此，我们报道了可生物降解的癌细胞膜包覆的介孔铜/锰硅酸盐纳米球（mCMSNs），其具有对癌细胞系的同型靶向能力，并通过单线态氧（O-1（2））的产生和谷胱甘肽（GSH）激活的芬顿反应增强ROS的产生，显示出优异的CDT/PDT协同治疗效果。我们证明mCMSNs能够通过催化内源性H2 O2分解为O-2来缓解肿瘤缺氧微环境，并进一步与O-2反应，在635 nm激光照射下产生毒性O-1（2）。GSH触发的mCMSNs生物降解可以同时产生Fenton样的Cu+和Mn 2+离子，并消耗GSH用于有效的羟基自由基（中心点OH）产生。同时也揭示了其对癌细胞的特异性识别和同型靶向能力。值得注意的是，缓解缺氧和GSH耗竭破坏了肿瘤微环境（TME）和细胞抗氧化防御系统，在体外和体内实现了卓越的癌症靶向治疗效果。癌细胞生长受到明显抑制。此外，释放的Mn 2+还可以作为癌症磁共振成像（MRI）的高级造影剂。因此，连同光敏剂、芬顿试剂提供者和MRI对比效应沿着TME的调节，允许mCMSN实现MRI监测的增强CDT/PDT协同治疗。它提供了一个范例，合理设计TME响应和ROS参与的治疗策略的基础上，一个单一的多金属硅酸盐纳米材料具有增强的抗癌作用。
The integration of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemo-dynamic therapy (CDT) holds great promise for enhanced anticancer effects. Herein, we report biodegradable cancer cell membrane-coated mesoporous copper/manganese silicate nanospheres (mCMSNs) with homotypic targeting ability to the cancer cell lines and enhanced ROS generation through singlet oxygen (O-1(2)) production and glutathione (GSH)-activated Fenton reaction, showing excellent CDT/PDT synergistic therapeutic effects. We demonstrate that mCMSNs are able to relieve the tumor hypoxia microenvironment by catalytic decomposition of endogenous H2O2 to O-2 and further react with O-2 to produce toxic O-1(2) with a 635 nm laser irradiation. GSH-triggered mCMSNs biodegradation can simultaneously generate Fenton-like Cu+ and Mn2+ ions and deplete GSH for efficient hydroxyl radical (center dot OH) production. The specific recognition and homotypic targeting ability to the cancer cells were also revealed. Notably, relieving hypoxia and GSH depletion disrupts the tumor microenvironment (TME) and cellular antioxidant defense system, achieving exceptional cancer targeting therapeutic effects in vitro and in vivo. The cancer cells growth was significantly inhibited. Moreover, the released Mn2+ can also act as an advanced contrast agent for cancer magnetic resonance imaging (MRI). Thus, together with photosensitizers, Fenton agent provider and MRI contrast effects along with the modulating of the TME allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy. It provides a paradigm to rationally design TME-responsive and ROS-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effects.