Intratumoral synthesis of nano-metalchelate for tumor catalytic therapy by ligand field-enhanced coordination

Bowen Yang; Heliang Yao; Han Tian; Zhiguo Yu; Yuedong Guo; Yuemei Wang; Jiacai Yang; Chang Chen; Jianlin Shi

doi:10.1038/s41467-021-23710-y

Intratumoral synthesis of nano-metalchelate for tumor catalytic therapy by ligand field-enhanced coordination

Nat Commun. 2021 Jun 7;12(1):3393. doi: 10.1038/s41467-021-23710-y.

Authors

Bowen Yang^{1

2}, Heliang Yao¹, Han Tian^{1

2}, Zhiguo Yu^{1

2}, Yuedong Guo^{1

2}, Yuemei Wang^{1

2}, Jiacai Yang^{1

2}, Chang Chen^{1

2}, Jianlin Shi³

Affiliations

¹ State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China.
² Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
³ State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China. jlshi@mail.sic.ac.cn.

Abstract

The iron gall ink-triggered chemical corrosion of hand-written documents is a big threat to Western cultural heritages, which was demonstrated to result from the iron gall (GA-Fe) chelate-promoted reactive oxygen species generation. Such a phenomenon has inspired us to apply the pro-oxidative mechanism of GA-Fe to anticancer therapy. In this work, we construct a composite cancer nanomedicine by loading gallate into a Fe-engineered mesoporous silica nanocarrier, which can degrade in acidic tumor to release the doped Fe³⁺ and the loaded gallate, forming GA-Fe nanocomplex in situ. The nanocomplex with a highly reductive ligand field can promote oxygen reduction reactions generating hydrogen peroxide. Moreover, the resultant two-electron oxidation form of GA-Fe is an excellent Fenton-like agent that can catalyze hydrogen peroxide decomposition into hydroxyl radical, finally triggering severe oxidative damage to tumors. Such a therapeutic approach by intratumoral synthesis of GA-Fe nano-metalchelate may be instructive to future anticancer researches.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / chemistry
Antineoplastic Agents / metabolism
Catalysis
Coordination Complexes / administration & dosage
Coordination Complexes / chemistry
Coordination Complexes / metabolism
Drug Carriers / chemistry
Female
Gallic Acid / administration & dosage*
Gallic Acid / chemistry
Gallic Acid / metabolism
HeLa Cells
Human Umbilical Vein Endothelial Cells
Humans
Hydrogen Peroxide / chemistry
Hydrogen Peroxide / metabolism
Hydrogen-Ion Concentration
Hydroxyl Radical / chemistry
Hydroxyl Radical / metabolism
Injections, Intravenous
Iron / administration & dosage*
Iron / chemistry
Iron / metabolism
Ligands
Metal Nanoparticles / administration & dosage*
Metal Nanoparticles / chemistry
Mice
Neoplasms / drug therapy*
Neoplasms / pathology
Oxidation-Reduction
Oxygen / metabolism
Silicon Dioxide / chemistry
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Coordination Complexes
Drug Carriers
Ligands
Hydroxyl Radical
Gallic Acid
Silicon Dioxide
Hydrogen Peroxide
Iron
Oxygen