声动力疗法
光热治疗
光敏剂
单线态氧
谷胱甘肽
纳米囊
光动力疗法
光热效应
生物物理学
氧化应激
丁硫胺
化学
纳米技术
纳米颗粒
癌症研究
材料科学
光化学
氧气
医学
有机化学
生物化学
生物
酶
作者
Jiajing Liu,Mengqi Li,Zhiyu Zhao,Xian Luo,Li Wang,Tingting Li,Cong Liu,Shengyu Wang,Ting Wu,Dong Kwon Yang,Yang Li,Peiyuan Wang,Jianghua Yan,Fanghong Luo
标识
DOI:10.1016/j.cej.2023.141427
摘要
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) via tetra-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 promote 1O2 generation efficiency for enhanced SDT. Furthermore, the released ATO could significantly reduce O2 consumption 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.
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