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Microenvironment-responsive piezoelectric nanoreactors integrate O2 and H2 generation for efficient tumor sonodynamic therapy
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DOI：10.1016/j.actbio.2026.05.014.png)
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Abstract
En 中文
Sonodynamic therapy (SDT) has emerged as a research hotspot in tumor therapy due to its non-invasiveness, non-toxicity and high penetrability, as it activates sonosensitizers to generate reactive oxygen species (ROS) for tumor cell ablation under ultrasound irradiation. However, its therapeutic efficacy is severely compromised by the rapid electron-hole recombination of sonosensitizers, tumor hypoxia and high intracellular glutathione (GSH) levels in the tumor microenvironment. Herein, we developed a nanoreactor AB@CZP@HO to achieve synergistic antitumor effects of SDT and hydrogen therapy. Based on carbon-doped hollow porous CZ, this material features unique carbon doping and oxygen vacancies that inhibit electron-hole recombination, thus enhancing its piezoelectric coefficient and ultrasound-induced ROS generation capacity. Pt atoms deposited on the CZ surface form CZP, whose catalase-like activity catalyzes the decomposition of intracellular hydrogen H2O2 to produce O2, alleviating tumor hypoxia and providing more substrates for SDT. The loaded ammonia borane with high hydrogen storage capacity enables high-load intratumoral hydrogen delivery and pH-responsive release. The released H2 disrupts the redox homeostasis and mitochondrial membrane integrity of tumor cells, synergizing with SDT. The surface-modified hyaluronic acid (HA) derivative HO depletes intratumoral GSH via affinity substitution reaction, further boosting SDT efficacy. This design integrates the rational fabrication of piezoelectric materials, tumor microenvironment remodeling and hydrogen therapy synergy, which collectively enhance the therapeutic efficacy of SDT.
Keywords:
Sonodynamic therapy
Piezoelectric nanoreactors
Tumor microenvironment remodeling
Hydrogen therapy
Reactive oxygen species
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