Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance.
Hai WangZan GaoXuanyou LiuPranay AgarwalShuting ZhaoDaniel W ConroyGuang JiJianhua YuChristopher P JaroniecZhenguo LiuXiongbin LuXiaodong LiXiaoming HePublished in: Nature communications (2018)
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.
Keyphrases
- reactive oxygen species
- multidrug resistant
- cell death
- papillary thyroid
- photodynamic therapy
- drug release
- gram negative
- dna damage
- poor prognosis
- acinetobacter baumannii
- fluorescent probe
- oxidative stress
- cell proliferation
- locally advanced
- combination therapy
- big data
- endoplasmic reticulum
- drug delivery
- squamous cell carcinoma
- young adults
- high resolution
- machine learning
- artificial intelligence
- pseudomonas aeruginosa