Near infrared light triggered nitric oxide releasing platform based on upconversion nanoparticles for synergistic therapy of cancer stem-like cells

Near infrared (NIR) light-driven nitric oxide (NO) release nano-platform based on upconversion nanoparticles (UCNPs) and light sensitive NO precursor Roussin's black salt (RBS) was fabricated to generate NO upon 808nm irradiation. The application of 808nm laser as the excitation source could achieve better penetration depth and avoid overheating problem. The combination of UCNPs and RBS could realize the on-demand release of NO at desired time and location by simply controlling the output of NIR laser. Cellular uptake results showed that more nanoparticles were internalized in cancer stem-like cells (CSCs) rather than non-CSCs. Therefore, a synergistic cancer therapy strategy to eradicate both CSCs and non-CSCs simultaneously was developed. Traditional chemo-drug could inhibit non-CSCs but has low killing efficiency in CSCs. However, we found that the combination of NO and chemotherapy could efficiently inhibit CSCs in bulk cells, including inhibiting mammosphere formation ability, decreasing CD44+/CD24- subpopulation and reducing tumorigenic ability. The mechanism studies confirmed that NO could not only induce apoptosis but also increase drug sensitivity by declining drug efflux in CSCs. This UCNPs-based platform may provide a new combinatorial strategy of NO and chemotherapy to improve cancer treatment.