Title: Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance.
Authors: Wang, Hai; Gao, Zan; Liu, Xuanyou; Agarwal, Pranay; Zhao, Shuting; Conroy, Daniel W; Ji, Guang; Yu, Jianhua; Jaroniec, Christopher P; Liu, Zhenguo; Lu, Xiongbin; Li, Xiaodong; He, Xiaoming
Published In Nat Commun, (2018 02 08)
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.
PubMed ID: 29422620
MeSH Terms: ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism; Adenosine Triphosphate/metabolism; Antineoplastic Agents/chemistry; Antineoplastic Agents/pharmacology; Cell Line, Tumor; Doxorubicin/pharmacology; Drug Resistance, Multiple*; Drug Resistance, Neoplasm*; Humans; MCF-7 Cells; Mitochondria/drug effects; Mitochondria/metabolism*; NAD/metabolism; Nanoparticles/chemistry; Oxidation-Reduction; Reactive Oxygen Species/metabolism*; Silicon Dioxide/chemistry