New progress has been made in the study of glucose metabolism intervention to sensitize tumor cells ferrozoticosis

Recently, Professor Zhai Guangxi and Associate Researcher Yang Xiaoye of the School of Pharmacy of Shandong University have made new progress in the study of glucose metabolism intervention in the study of ferrozosis in sensitized tumor cells, and the relevant research results were published in the international journal American Chemical Society Nano. Shandong University is an independent corresponding author unit.

Hemozotic activation is considered to be a powerful weapon in the treatment of cancer, and enhancing the sensitivity of tumor cells to ferrozosis is receiving more and more attention. However, certain iron-dead resistance mechanisms have long been overlooked, particularly abnormal metabolism of tumor cells.

Glucose metabolism intervention sensitizes tumor cells ferrozotic study Photo courtesy of Shandong University

According to reports, the research group proposed a model to enhance the activation of iron death by regulating sugar metabolism in tumor cells, and constructed a nanoplatform called PMVL. The platform is formed by coordinating clonidamine-loaded tannins with vanadium oxides and wrapped with tumor cell membranes modified by protein PD-L1 inhibitory peptides.

This study shows that vanadium in the PMVL nanoplatform has a mixed valence state, which causes iron death due to the change of vanadium’s self-cyclic valence state, a process that produces substances for lipid peroxidation accumulation and consumes glutathione for glutathione peroxidase inactivation.

Notably, clonidamine enhances ferrozois by inhibiting the pentose phosphate pathway and inhibits glutathione synthesis. In addition, glycolytic inhibition reduces intracellular lactic acid production, reduces the acidity of the tumor microenvironment, and inhibits immunosuppressive M2 macrophage polarization. In vitro and in vivo results showed that glucose metabolism intervention enhanced the iron death and immune activation of tumors, and significantly improved the synergistic therapeutic effect of tumors.

This work was supported by the National Science and Technology Major Project of “Major New Drug Creation”, the National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province, and the Taishan Industry Expert Program of Shandong Province. (Source: China Science News, Liao Yang, Che Huiqing)

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