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• Biodegradable CoSnO 3 nanocubes are employed as sonosensitizers and nanozymes. • GQD/CoSnO 3 is constructed by depositing GQD topoisomerases inhibitors on CoSnO 3. • Heterojunction-fabricated GQD/CoSnO 3 shows cascaded amplification of ROS generation. • Tumor-specific release of GQDs for chemotherapy is realized after completion of SDT. • GQD/CoSnO 3 achieves complete tumor eradication through chemotherapy, SDT, and NCT. Albeit nanozymes are widely applied for nanocatalytic therapy (NCT), the unsatisfactory catalytic activity of nanozymes accompanied by complex tumor microenvironment (TME) greatly pose a barrier to the therapeutic effect of NCT. Moreover, developing a high-efficiency nanozyme with biodegradability is still a huge challenge, which hinders their further clinical translation. Herein, pH-responsive biodegradable CoSnO 3 nanocubes are synthesized and employed as sonosensitizers and nanozymes due to their narrow bandgaps (1.6 eV) and Co2+/Sn4+-mediated multi-enzyme activities. After depositing the graphene quantum dot (GQD) topoisomerase inhibitors on CoSnO 3 nanocubes, the heterojunction-fabricated GQD/CoSnO 3 shows cascaded amplification of ROS generation, which is ascribed to the inhibition of electron-hole pair recombination, Co2+-mediated peroxidase (POD)-mimic catalytic reaction to generate OH, Co3+/Sn4+-mediated depletion of overexpressed GSH, and catalytic decomposition of endogenous H 2 O 2 for providing more O 2 for enhanced SDT. More importantly, GQD/CoSnO 3 heterojunctions are slowly degraded in the weakly acidic TME, resulting the tumor-specific release of GQDs after completion of SDT, which could induce DNA damage and cell apoptosis for chemotherapy to further enhanced the antitumor efficacy. The synergetic therapeutic efficacy of GQD/CoSnO 3 heterojunctions through chemotherapy, SDT, and NCT could realize "three-in-one" multimodal oncotherapy to completely eliminate tumors without recurrence. This work provides a paradigm of exploring pH-responsive biodegradable nanozymes as a drug carrier to realize tumor-specific drug release for enhanced SDT and NCT. [ABSTRACT FROM AUTHOR]

• Co 3 O 4 @TiO 2-x were synthesized for Z-scheme HJ-enhanced SDT-nanocatalytic therapy. • HJs enhanced SDT properties and triple enzyme-mimic activities of Co 3 O 4 @TiO 2-x. • Co2+ and Ti3+ ions catalyzed the Fenton-like reaction to generate more •OH. • Co3+ ions overcame GSH-mediated resistance to SDT and nanocatalytic therapy. • Complete tumor eradication was realized by Co 3 O 4 @TiO 2-x under US irradiation. Nanozymes have shown promising potential in cancer therapy owing to the advantages of low-cost, excellent stability, and high reproducibility. However, the inherent low catalytic activity of nanozymes and highly complex tumor microenvironment (TME) severely restricted the clinical applications of nanocatalytic therapy. Herein, we first reported a heterojunction (HJ)-enhanced nanocatalytic-sonodynamic therapy platform based on Co 3 O 4 @TiO 2-x Z-scheme HJs by depositing Co 3 O 4 nanoparticles (NPs) onto TiO 2-x nanosheets (NSs). Co 3 O 4 @TiO 2-x HJs not only exhibited excellent ultrasound (US)-triggered reactive oxygen species (ROS) generation ability, but also possessed triple enzyme-mimic activities (peroxidase-mimic, catalase-mimic, and GSH depletion activities) to realize the amplification of ROS levels and relieve tumor hypoxia. More importantly, the triple enzyme-mimic activities and sonodynamic properties of single-component Co 3 O 4 or TiO 2-x were greatly enhanced by the construction of Z-scheme HJs owing to the accelerate carrier transfer process and improved spatial separation dynamics of US-generated electron-hole pairs. The synergetic therapeutic effect of Co 3 O 4 @TiO 2-x through HJ-enhanced nanocatalytic-sonodynamic therapy could achieve complete tumor eradication without recurrence. Our work will open up a promising approach to engineer semiconductor HJs with both sonodynamic and enzyme-mimic activities for enhanced nanocatalytic-sonodynamic combination therapy. [ABSTRACT FROM AUTHOR]