Mitochondria-specific nanocatalysts for chemotherapy-augmented sequential chemoreactive tumor therapy

The therapeutic modality of “chemotherapy-augmented sequential chemoreactive therapy” based on the designed mitochondria-specific nanocatalyst composed of cisplatin prodrug and gallic acid-ferrous (GA-Fe(II)) nanocomposites achieves distinct catalytic cancer-therapeutic performance. The bioactive cisplatin elevates the endogenous H2O2 level through the cascaded reactions, and the GA-Fe(II) nanocomposites with sustainable Fenton catalytic activity subsequently catalyzes H2O2 into hydroxyl radicals to substantially inhibit tumor progression.

Abstract:

Endogenic tumor chemodynamic therapy (CDT) is emerging as a tumor-therapeutic strategy featuring in situ treatments with high efficiency and specificity based on the Fenton reaction principle. Considering the limitation of monotherapy and relatively insufficient intracellular level of endogenous hydrogen peroxide (H2O2) in tumor tissues, a mitochondria-specific nanocatalyst composed of cisplatin prodrug and gallic acid-ferrous (GA-Fe(II)) nanocomposites is successfully fabricated to fulfill chemotherapy-augmented sequential chemoreactive tumor therapy. The bioactive cisplatin elevates the level of endogenous H2O2 through the activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-related cascaded reactions, and the GA-Fe(II) nanocomposites possessing sustainable Fenton catalytic activity subsequently catalyzes H2O2 into highly reactive and toxic hydroxyl radicals to substantially inhibit tumor progression. Especially, this mitochondria-specific nanocatalyst amplifies oxidative stress, stimulates mitochondrial dysfunction, downregulates AKT/mTOR signaling and finally induces cell autophagic death. Both in vitro and in vivo measurements verify that the chemotherapy-augmented sequential chemoreactive nanotherapy based on the mitochondria-specific nanocatalyst implements excellent anticancer efficiency and avoids undesired side effects. This work reveals the enormous potential of chemotherapy-augmented CDT for combating tumors.

Author list:

Hui Huang, Caihong Dong*, Meiqi Chang, Li Ding, Liang Chen, Wei Feng*, Yu Chen*

How to cite:

H. Huang, C. Dong, M. Chang, L. Ding, L. Chen, W. Feng, Y. Chen, Exploration 2021, 1, 50-60.
https://doi.org/10.1002/EXP.20210149