Fusiform-Like Copper(II)-Based Metal-Organic Framework through Relief Hypoxia and GSH-Depletion Co-Enhanced Starvation and Chemodynamic Synergetic Cancer Therapy.

Abstract

The therapeutic effect of traditional chemodynamic therapy (CDT) agents is severely restricted by their weakly acidic pH and glutathione (GSH) overexpression in the tumor microenvironment. Here, fusiform-like copper(II)-based tetrakis(4-carboxy phenyl)porphyrin (TCPP) nanoscale metal-organic frameworks (nMOFs) were designed and constructed for the first time (named PCN-224(Cu)-GOD@MnO2). The coated MnO2 layer can not only avoid conjugation of glucose oxidase (GOD) to damage normal cells but also catalyzes the generation of O2 from H2O2 to enhance the oxidation of glucose (Glu) by GOD, which also provides abundant H2O2 for the subsequent Cu+-based Fenton-like reaction. Meanwhile, the Cu2+ chelated to the TCPP ligand is converted to Cu+ by the excess GSH in the tumor, which reduces the tumor antioxidant activity to improve the CDT effect. Next, the Cu+ reacts with the plentiful H2O2 by enzyme catalysis to produce a toxic hydroxyl radical (•OH), and singlet oxygen (1O2) is synchronously generated from combination with Cu+, O2, and H2O via the Russell mechanism. Furthermore, the nanoplatform can be used for both TCPP-based in vivo fluorescence imaging and Mn2+-induced T1-weighted magnetic resonance imaging. In conclusion, fusiform-like PCN-224(Cu)-GOD@MnO2 nMOFs facilitate the therapeutic efficiency of chemodynamic and starvation therapy via combination with relief hypoxia and GSH depletion after acting as an accurate imaging guide.

• Authors: Zhao Wang, Bin Liu, Qianqian Sun, Shuming Dong, Ye Kuang, Yushan Dong, Fei He, Shili Gai, Piaoping Yang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 12 Issue 15 Pg. 17254-17267 (Apr 15 2020) ISSN: 1944-8252 [Electronic] United States
• PMID: 32227859 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Fenton's reagent
• Manganese Compounds
• Metal-Organic Frameworks
• Oxides
• Porphyrins
• tetracarboxyphenylporphine
• Singlet Oxygen
• manganese oxide
• Copper
• Hydrogen Peroxide
• Iron
• Glucose Oxidase
• Glutathione

Topics

• Animals
• Antineoplastic Agents (chemistry, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Copper (chemistry)
• Female
• Glucose Oxidase (chemistry, metabolism)
• Glutathione (chemistry, metabolism)
• Humans
• Hydrogen Peroxide (chemistry, metabolism)
• Iron (chemistry)
• Magnetic Resonance Imaging
• Manganese Compounds (chemistry)
• Metal-Organic Frameworks (chemistry)
• Mice
• Neoplasms (diagnostic imaging, drug therapy)
• Oxidation-Reduction
• Oxides (chemistry)
• Porphyrins (chemistry)
• Singlet Oxygen (metabolism)