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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]