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

ChemMedChem. 2021 Jul 20;16(14):2278-2286. doi: 10.1002/cmdc.202100108. Epub 2021 May 4.

Abstract

Chemodynamic therapy (CDT) is an effective tumor treatment strategy in which FeII reacts with hydrogen peroxide (H2 O2 ) in tumor cells to produce highly toxic hydroxyl radical (. OH) through the Fenton reaction. However, the content of endogenous H2 O2 in cells is limited, and the reaction between FeIII and H2 O2 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-FeIII ) for the enhanced CDT of tumors, in which the polyphenolic compound- tannic acid (TA) and FeIII formed a TA-Fe nano-coating on the surface of calcium peroxide (CaO2 ) nanospherical aggregates. When the CaO2 @TA-FeIII nanoconjugates reach the tumor site, the CaO2 contained in the nanoconjugates produces H2 O2 after disintegration in tumor cells, and the carried TA rapidly reduces FeIII to FeII , solving the two major shortcomings in CDT of (1) insufficient content of H2 O2 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-FeIII nanoconjugates can effectively kill cancer cells and display an excellent tumor therapeutic effect. We believe that the CaO2 @TA-FeIII nanoconjugates are a promising new nano-platform for highly effective tumor treatment.

Keywords: Calcium overload; Calcium peroxide; Chemodynamic therapy; Fenton reaction; Tannic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Ferric Compounds / chemistry
  • Ferric Compounds / pharmacology*
  • Mice
  • Nanoparticles / chemistry*
  • Optical Imaging
  • Particle Size
  • Peroxides / chemistry
  • Peroxides / pharmacology*
  • Structure-Activity Relationship
  • Surface Properties
  • Tannins / chemistry
  • Tannins / pharmacology*

Substances

  • Antineoplastic Agents
  • Ferric Compounds
  • Peroxides
  • Tannins
  • calcium peroxide