A CaO2@Tannic Acid-FeIII Nanoconjugate for Enhanced Chemodynamic Tumor Therapy

Chemodynamic therapy (CDT) is an effective tumor treatment strategy in which Fe^II reacts with hydrogen peroxide (H₂O₂) in tumor cells to produce highly toxic hydroxyl radical (^.OH) through the Fenton reaction. However, the content of endogenous H₂O₂ in cells is limited, and the reaction between Fe^III and H₂O₂ is inefficient, greatly limiting the efficiency of the Fenton reaction and reducing the effectiveness of tumor treatment. Therefore, in this work, we designed and synthesized a new type of nano-system (CaO₂@TA-Fe^III) for the enhanced CDT of tumors, in which the polyphenolic compound- tannic acid (TA) and Fe^III formed a TA-Fe nano-coating on the surface of calcium peroxide (CaO₂) nanospherical aggregates. When the CaO₂@TA-Fe^III nanoconjugates reach the tumor site, the CaO₂ contained in the nanoconjugates produces H₂O₂ after disintegration in tumor cells, and the carried TA rapidly reduces Fe^III to Fe^II, solving the two major shortcomings in CDT of (1) insufficient content of H₂O₂ in cancer cells, and (2) low catalytic efficiency of the Fenton reaction. Additionally, the ^.OH produced in the Fenton reaction induces oxidative stress for the tumor cells, promoting the occurrence of the “calcium overload” process, and thereby accelerating the death of tumor cells. Experimental results in vitro and in vivo showed that CaO₂@TA-Fe^III nanoconjugates can effectively kill cancer cells and display an excellent tumor therapeutic effect. We believe that the CaO₂@TA-Fe^III nanoconjugates are a promising new nano-platform for highly effective tumor treatment.