Extended Data Fig. 6: Pharmacokinetics, biodistribution, and antitumour efficacy of NP3.
a, The blood clearance kinetics during 24 h post-intravenous administration of Ce6, Ctrl-NP3, and NP3 (Ce6-equiv. dose, 2.5 mg/kg), respectively. b-d, In vivo distribution of Ce6 (b), Ctrl-NP3 (c), and NP3 (d) in main organs and tumours during 24 h post-intravenous administration of Ce6, Ctrl-NP3, and NP3 (Ce6-equiv. dose, 2.5 mg/kg), respectively. e, In situ biodistribution of NP3 and Ctrl-NP3 in specific time points (6 h and 24 h) after intravenous injection into MDA-MB-231 tumour-bearing nude mice, at a Ce6 dose of 2.5 mg/kg, respectively. The white cycles indicate the tumour regions. f, Fluorescence of tumours at different time points. g, In situ biodistribution of Ce6 in specific time points (6 h and 24 h) after intravenous injection into MDA-MB-231 tumour-bearing nude mice, at a dose of 2.5 mg/kg. The white cycles indicate the tumour regions. h, Fluorescence of tumours at different time points. i, In situ biodistribution of Ce6, Ctrl-NP3 and NP3 in specific time points (6 h and 24 h) after intravenous injection into 4T1 tumour-bearing mice, at a dose of Ce6 2.5 mg/kg, respectively. The white cycles indicate the tumour regions. j, Fluorescence of tumours at different time points. k,l, Fluorescence images (k) and quantitative calculation (l) of tumour and different organs at 24 h after intravenous administration of NP3 or Ctrl-NP3 (Ce6-equiv. dose, 2.5 mg/kg). m,n, Fluorescence images (m) and quantitative calculation (n) of tumour and different organs at 24 h after intravenous administration of Ce6 at a dose of 2.5 mg/kg. o, Tumour inhibition rate of PBS (+), Ce6 (L-), Ctrl-NP3 (L-), NP3 (L-), Ce6 (L+), Ctrl-NP3 (L+), and NP3(L+) in MDA-MB-231 tumour-bearing mice model, respectively. p, Quantification of the percentages of TUNEL positive area in tumours with different treatments in MDA-MB-231 tumour-bearing mice model. Three random fields were observed for each mouse under the microscope. q, H&E staining images for histological analysis of major organs (heart, liver, kidney, and spleen) collected from MDA-MB-231 tumour-bearing mice in different treatment groups. Scale bars, 100 μm. r,s, Effect of the PDT therapy of NP3 on EV numbers in circulation in mice. r, 4T1 tumour-bearing BALB/c mice were treated with NP3 at a Ce6 dose of 2.5 mg/kg and 660 nm laser (200 mW/cm2, 5 min) on selected days post-inoculation. s, Relative change in EV numbers in circulation post NP3/light treatment, as measured by NTA. The results indicated that the total number of EVs in circulation remained consistent before and after NP3/light treatment. In a-j,m-n,p, n = 3 mice; in k,l, n = 1 mouse; in o,s, n = 4 mice. Data are presented as the mean ± s.d. Statistical significance was calculated via unpaired two-tailed Student’s t-test (f, h, j, o) and one-way ANOVA with Tukey’s multiple comparisons test (p, s). In q, the representative images are shown from three mice per group.
