Boosting tumor treatment by dredging the hurdles of chemodynamic therapy synergistic ion therapy.

• Hybrid nanoparticle with H 2 O 2 self-supply and iron ion self-circulation properties dredge the hurdles of CDT. • Photothermal accelerates H 2 O 2 /Fe3+ self-supply and improve efficiency of CDT. • To be applied for enhanced CDT synergistic antitumor ion therapy. Although chemodynamic therapy (CDT) holds the advantage of tumor treatment by generating hydroxyl radicals (·OH) without the participation of O 2 , insufficient H 2 O 2 and the hindered Fe ion circulation remain major hurdles for its clinical application. Herein, we developed a hybrid nanoparticle with H 2 O 2 self-supply and iron ion self-circulation properties for enhanced CDT. Through encapsulation of CaO 2 with ZIF-8 and in situ assembled Fe3+/TA (tannic acid) on the surface, the hybrid nanoparticles (CaO 2 @ZIF8@MPN) were prepared. The Fe3+/TA coating could dissociate in response to lysosomal acidity, and release Fe3+ and TA subsequently. Significantly, the unprotected CaO 2 can be degraded to H 2 O 2 and Ca2+, providing sufficient materials for CDT and resulting in a Ca2+ "storm" for ion therapy. Meanwhile, TA could convert Fe3+ to Fe2+, realizing a self-circulation for promoting the sustained generation of ·OH. Interestingly, Fe3+/TA coating endows the nanoparticles with photothermal property, which accelerated the degradation and further improved the efficiency of Fenton reaction, obtaining 77.7% of tumor growth inhibited rate without obvious adverse effect in tumor-bearing mice. Our findings showed CaO 2 @ZIF8@MPN had potential to be applied for enhanced CDT synergistic antitumor ion therapy. [ABSTRACT FROM AUTHOR]