(Peer-Reviewed) Cascade-responsive Nanobomb with domino effect for anti-tumor synergistic therapies
Yang Liu 刘洋 ¹ ², Yinghui Wang 王樱蕙 ¹, Shuyan Song 宋术岩 ¹ ², Hongjie Zhang 张洪杰 ¹ ² ³
¹ State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China 中国科学院 长春应用化学研究所 稀土资源利用国家重点实验室
² School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China 中国科学技术大学 应用化学与工程学院
³ Department of Chemistry, Tsinghua University, Beijing 100084, China 清华大学 化学系
National Science Review, 2021-08-09
Abstract
The development of reactive oxygen species (ROS) generation agents that can selectively produce sufficient ROS at the tumor site without external energy stimulation is of great significance for the further clinical application of ROS-based therapies.
Herein, we designed a cascade-responsive ROS nanobomb (ZnO₂@Ce6/CaP@CPPO/BSA, designated as Z@Ce6/CaP@CB) with domino effect and without external stimulation for the specific generation of multiple powerful ROS storms at the tumor site. The CaP shell and ZnO₂ core gradually degrade and release Ca²⁺, Zn²⁺, and hydrogen peroxide (H₂O₂) under acid stimulation.
On the one hand, Zn²⁺ can enhance the generation of endogenous superoxide anions (·O₂⁻) and H₂O₂ through the inhibition of the mitochondrial electron transport chain (ETC). On the other hand, the generation of large amounts of exogenous H₂O₂ can cause oxidative damage to tumor cells and further activate bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO)-mediated chemiexcited photodynamic therapy.
In addition, the oxidative stress caused by the generated ROS can lead to the uncontrolled accumulation of Ca²⁺ in cells and further result in Ca²⁺ overload-induced cell death. Therefore, the introduction of Z@Ce6/CaP@CB nanobombs triggered the 'domino effect' that caused multiple heavy ROS storms and Ca²⁺ overload in tumors and effectively activated anti-tumor immune response.
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