Fig. 3

Overcoming drug resistance by targeted production of reactive oxygen species in mitochondria. a When irradiated with NIR laser, the LSC nanoparticles can specifically produce reactive oxygen species (ROS) in mitochondria. This oxidizes NADH into NAD⁺ to inhibit the production of ATP, which stops the function of the efflux pumps and overcomes the cancer drug resistance. b Representative TEM images of NCI/RES-ADR multidrug-resistant cells incubated in medium without (Control) or with LSC-D nanoparticles. M indicates the mitochondria. Arrows indicate the LSC-D nanoparticles in mitochondria. E/L indicates endosome/lysosome. Scale bar: 2 and 0.3 μm for low and high magnification images, respectively. c Confocal images of NCI/RES-ADR cells treated with LSC and LSC-D nanoparticles showing the specific production of ROS in mitochondria. Scale bar: 10 μm. d Quantitative data on ROS production in NCI/RES-ADR cells under various conditions. Error bars represent s.d. (n = 3). The LSC + L group is compared with the LSC group with the same LSC concentration, as well as the control (medium) and laser (alone) groups. *p < 0.05 (Kruskal–Wallis H-test). e Relative NADH in NCI/RES-ADR cells showing the decrease of NADH in cells treated with LSC nanoparticles with laser irradiation (LSC + L, 1 W cm⁻² for 1 min). Error bars represent s.d. (n = 3). The LSC + L group is compared with the LSC group with the same LSC concentration, as well as the control (medium) and laser (alone) groups. *p < 0.05 (Kruskal–Wallis H-test). f Consumption of ATP by the membrane proteins isolated from NCI/RES-ADR cells showing the transmembrane efflux pumps are not bound with ATP in the cells treated with LSC + L so that significantly more ATP can be consumed/bound by them. Error bars represent s.d. (n = 3). The LSC + L group is compared with the LSC group with the same LSC concentration, as well as the control (medium) and laser (alone) groups. *p < 0.05 (Kruskal–Wallis H-test)