Recently, Professor Luo Yu from the School of Chemistry and Chemical Engineering guided master's students Zhu Lichao and Peng Renmiao to publish research papers titled High efficiency Carriers' Separation Strategy Based on Ultrasmall Bandgap CuWO4 Sono enhancers GSH Antenna for Cuproptosis Cascade Immunotherapy and Cascade amplified Oxidative Stress via Bandgap Tuned KBiO3 Perovskite for Cancer Therapy in academic journals Advanced Science (Top of the First District of the Chinese Academy of Sciences, Impact Factor 14.3) and Small (Second District of the Chinese Academy of Sciences, Impact Factor 13.0).
Sonodynamic therapy (SDT) is a promising cancer treatment due to its ability to utilize ultrasound (US) to activate sonosensitizers, generating reactive oxygen species (ROS) for tumor suppression. High-valence bismuth, known for its unique photoacoustic properties and biocompatibility, has shown great potential when combined with SDT. However, conventional sonosensitizers with large bandgaps and electron-hole recombination have limited SDT's effectiveness. Herein, a bismuth-based piezoelectric sonosensitizer is developed, DSPE-PEG 2000-modified KBiO3 (KBP), which features a reduced bandgap (1.9 eV). This facilitates electron transfer and depletes glutathione in the tumor microenvironment. Under the US, the piezoelectric sonosensitizer KBP generates a significant amount of ROS, leading to cancer cell pyroptosis via the ROS-NLRP3-Caspase-1-GSDMD pathway. Both in vitro and in vivo experiments demonstrated that the piezoelectric SDT treatment can effectively inhibit tumor growth. This research offers a novel approach to cancer treatment by leveraging the advantages of piezoelectric SDT, demonstrating promising clinical potential for tumor inhibition.
The spatiotemporal sequential treatment strategy of promoting rapid separation of charge carriers, amplifying oxidative stress, increasing the low content of intracellular Cu, enhancing cuproptosis, and cascading activation of immunotherapy is considered one of the most effective techniques for improving the comprehensive therapy of tumors. Herein, copper tungstate (CuWO₄, CWO) nanoparticles with ultrasmall bandgap (1.71 eV) is developed as both piezoelectric-catalysis agents and copper nanocarriers for synergistic sono-enhanced cuproptosis. Owing to the unique bandgap microstructure, exposure to ultrasound (US) significantly increase the generation of reactive oxygen species (ROS) and the release of Cu2+ from CWO. Additionally, ≈60% of glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) are consumed in situ, leading to oxidative stress, ferroptosis, and cuproptosis in cancer cells. This cascading approach induces substantial mitochondrial dysfunction and the release of damage-associated molecular patterns (DAMPs), which promotes immunogenic cell death (ICD) and augments antitumor immunity. Both in vitro and in vivo studies have shown that this sono-enhanced cuproptosis-based therapy could effectively suppress tumor growth. Overall, this study investigates a novel Structure-Function therapeutic approach that combines piezoelectric catalysis, ferroptosis, cuproptosis, and cascade activation of immune regulation, opening up new possibilities for addressing the challenges associated with conventional cuproptosis therapy.
This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 52272280, 52302357, 32401174), Shanghai Shuguang Plan (No. 22SG53), and the Construction Project of Shanghai Engineering Research Center of Pharmaceutical Intelligent Equipment (20DZ2255900).