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.

Details

Title
Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance
Author
Wang, Hai 1 ; Gao, Zan 2   VIAFID ORCID Logo  ; Liu, Xuanyou 3 ; Agarwal, Pranay 4 ; Zhao, Shuting 4 ; Conroy, Daniel W 5 ; Ji, Guang 6   VIAFID ORCID Logo  ; Yu, Jianhua 7 ; Jaroniec, Christopher P 5   VIAFID ORCID Logo  ; Liu, Zhenguo 8 ; Lu, Xiongbin 9 ; Li, Xiaodong 2 ; He, Xiaoming 10   VIAFID ORCID Logo 

 Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA 
 Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville, VA, USA 
 Division of Cardiovascular Medicine, Center for Precision Medicine, University of Missouri School of Medicine, Columbia, MO, USA 
 Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA 
 Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA 
 Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China 
 Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Division of Hematology, The Ohio State University, Columbus, OH, USA 
 Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Division of Cardiovascular Medicine, Center for Precision Medicine, University of Missouri School of Medicine, Columbia, MO, USA 
 Department of Medical and Molecular Genetics and Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA 
10  Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA 
Pages
1-16
Publication year
2018
Publication date
Feb 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1999660168
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.