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.
Highlights
Multidrug resistance is a major challenge to cancer chemotherapy
To understand the possible molecular mechanisms of the lipid membrane-coated silicacarbon (LSC) + L treatment in sensitizing the drug-resistant cells to cancer therapy, we investigated the expression of two stress-related proteins in the NCI/RES-ADR cells first
The expression of heat shock factor-1 (HSF-1) that is commonly thought to be associated with HSP7040, is decreased at 12 h after the LSC + L treatment
Summary
The multidrug resistance phenotype is associated with the overexpression of the adenosine triphosphate (ATP)-driven transmembrane efflux pumps in cancer cells. 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. An important advance in the understanding of cancer drug resistance is the identification of P-glycoprotein (P-gp) and other related transporters-based efflux pumps in the plasma membrane of some cancer cells. Inhibiting the function of ABC transporters should be an effective strategy to overcome cancer drug resistance. As ATP is indispensable for the efflux pumps/ transporters to function, cancer drug resistance may be overcome by inhibiting the production of ATP in cancer cells[11].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
