Thermally Gated Dual-Cascade Nanozyme for Enhanced Mild-Temperature Photothermal Therapy
Shuyu Wang1,2, Shenghui Wang1, Mengyuan Cao1
1Nanozyme Laboratory in Zhongyuan, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 7, 2025
Summary
This study introduces a novel nanozyme system to overcome heat resistance in mild-temperature photothermal therapy (mPTT) by dual suppressing heat shock protein 70 (HSP70), enhancing cancer treatment efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Mild-temperature photothermal therapy (mPTT) offers precise cancer treatment but faces limitations due to heat shock protein 70 (HSP70)-mediated thermotolerance.
- Tumor cells can survive sublethal heating via HSP70, reducing mPTT effectiveness.
Purpose of the Study:
- To develop a thermo-responsive cascade nanozyme system (Ru-GOx-PNN) to enhance mPTT by dual suppressing HSP70.
- To overcome thermotolerance and improve the therapeutic efficacy of mPTT for cancer treatment.
Main Methods:
- Integration of a Ru-doped porous carbon framework as a photothermal transducer and nanozyme.
- Immobilization of glucose oxidase (GOx) to generate H2O2 for cascade reactions.
- Utilizing a thermosensitive PNN hydrogel for controlled substrate access and active site exposure within the mPTT window.
Main Results:
- The GOx-POD cascade generated hydroxyl radicals, inducing lipid peroxidation and destabilizing HSP70.
- The GOx-CAT cascade consumed glucose and reduced ATP synthesis, further suppressing HSP70 expression.
- Inhibition of HSP70 relieved its restraint on c-Jun N-terminal kinase signaling, amplifying apoptosis and enhancing mPTT efficacy.
Conclusions:
- The Ru-GOx-PNN system effectively overcomes thermal resistance in mPTT.
- This cascade catalytic nanozyme platform demonstrates potential for safe, efficient, and precise tumor therapy, especially for esophageal squamous cell carcinoma (ESCC).
