(A) In vivo fluorescence imaging of IDDHN distribution in 4T1 breast cancer-bearing mice (Ex. 780 nm; Em. 845 nm). (B) Ex vivo imaging of tumors and other tissues at 36 h post treatment. (C) ROI analysis of ICG fluorescence signals from the tumors and normal tissues (means ± SD, n = 3, *P < 0.05, ***P < 0.001). (D) Infrared thermal imaging of laser irradiation-induced temperature elevation in tumor region of 4T1 breast cancer-bearing mice post-injection of 5% glucose, IDD, IDDH or IDDHN. (E) Laser-enhanced NO release of IDDHN triggered deep tumor penetration of IDDHN, DAPI channel (blue), Cy3-tagged CD34 channel (red) and DOX channel (green), scale bars represent 50 mm. (F) Semi-quantitative intensity of DOX fluorescence signals from the tumors (means ± SD, n = 3, ***P < 0.001). (G) Extravasation of Evans blue induced by NO donor and laser irradiation of IDDHN in 4T1 tumor bearing mice (means ± SD, n = 3, *P < 0.05, ***P < 0.001). (Reproduced with permission from [30]. Copyright 2018 Elsevier).