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

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.

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Cited by papers we hold 5

• Unraveling mitochondria‐targeting reactive oxygen species modulation and their implementations in cancer therapy by nanomaterials · 2023
  No notice
• Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction · 2022
  No notice
• Nanoparticles in Clinical Translation for Cancer Therapy · 2022
  No notice
• ROS in cancer therapy: the bright side of the moon · 2020
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• Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance · 2020
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