Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance

Hai Wang, Zan Gao, Xuanyou Liu, Pranay Agarwal, Shuting Zhao, Daniel W. Conroy, Guang Ji, Jianhua Yu, Christopher P. Jaroniec, Zhenguo Liu, Xiongbin Lu, Xiaodong Li () and Xiaoming He ()
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Hai Wang: The Ohio State University
Zan Gao: University of Virginia
Xuanyou Liu: University of Missouri School of Medicine
Pranay Agarwal: The Ohio State University
Shuting Zhao: The Ohio State University
Daniel W. Conroy: The Ohio State University
Guang Ji: Shanghai University of Traditional Chinese Medicine
Jianhua Yu: The Ohio State University
Christopher P. Jaroniec: The Ohio State University
Zhenguo Liu: The Ohio State University
Xiongbin Lu: Indiana University School of Medicine
Xiaodong Li: University of Virginia
Xiaoming He: The Ohio State University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Multidrug resistance is a major challenge to cancer chemotherapy. The multidrug resistance phenotype is associated with the overexpression of the adenosine triphosphate (ATP)-driven transmembrane efflux pumps in cancer cells. Here, we report a lipid membrane-coated silica-carbon (LSC) hybrid nanoparticle that targets mitochondria through pyruvate, to specifically produce reactive oxygen species (ROS) in mitochondria under near-infrared (NIR) laser irradiation. The ROS can oxidize the NADH into NAD+ to reduce the amount of ATP available for the efflux pumps. The treatment with LSC nanoparticles and NIR laser irradiation also reduces the expression and increases the intracellular distribution of the efflux pumps. Consequently, multidrug-resistant cancer cells lose their multidrug resistance capability for at least 5 days, creating a therapeutic window for chemotherapy. Our in vivo data show that the drug-laden LSC nanoparticles in combination with NIR laser treatment can effectively inhibit the growth of multidrug-resistant tumors with no evident systemic toxicity.

Date: 2018
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DOI: 10.1038/s41467-018-02915-8

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