Gene interfered-ferroptosis therapy for cancers

Jinliang Gao, Tao Luo and Jinke Wang ()
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Jinliang Gao: Southeast University
Tao Luo: Southeast University
Jinke Wang: Southeast University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis.

Date: 2021
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DOI: 10.1038/s41467-021-25632-1

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