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

Although chemodynamic therapy (CDT) holds the advantage of tumor treatment by generating hydroxyl radicals (·OH) without the participation of O2, insufficient H2O2 and the hindered Fe ion circulation remain major hurdles for its clinical application. Herein, we developed a hybrid nanoparticle with H2O2 self-supply and iron ion self-circulation properties for enhanced CDT. Through encapsulation of CaO2 with ZIF-8 and in situ assembled Fe3+/TA (tannic acid) on the surface, the hybrid nanoparticles (CaO2@[email protected]) were prepared. The Fe3+/TA coating could dissociate in response to lysosomal acidity, and release Fe3+ and TA subsequently. Significantly, the unprotected CaO2 can be degraded to H2O2 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 CaO2@[email protected] had potential to be applied for enhanced CDT synergistic antitumor ion therapy.