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Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance.
- Source :
-
Nature communications [Nat Commun] 2018 Feb 08; Vol. 9 (1), pp. 562. Date of Electronic Publication: 2018 Feb 08. - Publication Year :
- 2018
-
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 <superscript>+</superscript> 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.
- Subjects :
- 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
Humans
MCF-7 Cells
Mitochondria drug effects
NAD metabolism
Nanoparticles chemistry
Oxidation-Reduction
Silicon Dioxide chemistry
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Mitochondria metabolism
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 29422620
- Full Text :
- https://doi.org/10.1038/s41467-018-02915-8