GSH-responsive and O2-economizing virus-like nanocapsule for photothermal-augmented sonodynamic therapy
GSH-responsive and O2-economizing virus-like nanocapsule for photothermal-augmented sonodynamic therapy
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DOI：
10.1016/j.cej.2023.141427
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发表时间：
2023-01
影响因子：
15.1
通讯作者：
Jiajing Liu;Mengqing Li;Zhiyu Zhao;Xian Luo;Li Wang;Tingting Li;Cong Liu;Shengyu Wang
中科院分区：
文献类型：
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作者：
Jiajing Liu;Mengqing Li;Zhiyu Zhao;Xian Luo;Li Wang;Tingting Li;Cong Liu;Shengyu Wang
与光动力疗法相比，声动力疗法（SDT）因其更大的组织穿透深度和更低的副作用而受到越来越多的关注。然而，肿瘤微环境的缺氧和单一疗法的局限性仍然严重阻碍了其治疗效果。本文制备了一种可生物降解的谷胱甘肽耗竭病毒激发纳米胶囊，以实现节约o2的光热增强声动力治疗。该纳米胶囊由聚多巴胺（PDA）内核和四硫化物桥接的病毒样介孔二氧化硅/环状RGD壳构成，可以有效地封装“氯e6- c -15-乙基酯”（HB，一种新型光敏剂）和阿托瓦醌（ATO，一种线粒体电子传输链抑制剂）。由于纳米胶囊具有病毒样的表面辅助活性靶向，可以有效地在肿瘤组织内积累，并迅速侵入肿瘤细胞。然后，在细胞内过量产生谷胱甘肽（GSH）的维生素a-硫化物-硫醇交换作用下，硅壳分解，持续释放ATO和HB，同时消耗GSH，削弱肿瘤细胞的抗氧化自卫机制。在超声（US）照射下，HB可以有效地产生单线态氧（1O2）用于SDT，而在808 nm激光照射下，PDA核心先前升高的温度可以提高10o2的产生效率，以增强SDT。此外，释放的ATO可以通过抑制线粒体呼吸，减轻缺氧微环境，放大氧化应激，从而显著减少o2的消耗。因此，所设计的用于臭氧节约光热增强声动力治疗的纳米胶囊为肿瘤根除提供了一种有前途的策略。
Compared to photodynamic therapy, sonodynamic therapy (SDT) has received increased attention due to higher tissue penetrative depth and low side effects. However, the hypoxia tumor microenvironment and monotherapy limitation still severely hindered its therapeutic effect. Herein, a biodegradable glutathione-depletion virus-inspired nanocapsule is prepared to achieve O2-economizing photothermal-augmented sonodynamic therapy. The nanocapsule is constructed by polydopamine (PDA) core and tetra-sulfide-bridged virus-like mesoporous silica/cyclic RGD shell, which could efficiently encapsulate both “chlorin e6-C-15-ethyl ester” (HB, a new photosensitizer) and atovaquone (ATO, a mitochondrial electron-transport-chain inhibitor). Owing to virus-like surface-assisted active targeting, the nanocapsule could efficiently accumulate within tumor tissues and rapidly invade the tumor cells. Afterwards, the silica shell would be decomposed under intracellular overproduced glutathione (GSH)viatetra-sulfide-thiol exchange to sustainedly release both ATO and HB while depleting GSH to weaken the antioxidant self-defense mechanism of tumor cells. Upon ultrasound (US) irradiation, the HB could efficiently generate singlet oxygen (1O2) for SDT, while the previously elevated temperature from the PDA core upon 808 nm laser irradiation could promote1O2generation efficiency for enhanced SDT. Furthermore, the released ATO could significantly reduce O2consumption by restraining the mitochondrial respiration to alleviate the hypoxic microenvironment to amplify oxidative stress. Therefore, the designed nanocapsule for O2-economized photothermal-augmented sonodynamic therapy could provide a promising strategy for tumor eradication.