In vivo enhanced therapeutic effect and lung metastasis suppression of EXO-DVDMS-SDT in 4T1-xenograft mice. (A) Tumor growth curves of different groups of 4T1 tumor-bearing mice (n = 6). ∗∗p < 0.01 versus control, ##p < 0.01 versus Free-DVDMS + US1+US2, && p < 0.01 versus EXO-DVDMS + US2. (B) Tumor weight inhibition ratio at the 12th day of different treatment groups. ∗∗p < 0.01 between different groups. (C) H&E stained images of tumor sections collected from different treated groups of mice. Bar = 50 μm. (D) Immunohistochemistry detection for PCNA after different treatments. Bar = 50 μm. (E) In situ apoptosis by TUNEL assay. Bar = 50 μm. (F) Photos of lungs after soaking in Bouin's solution showing spontaneous pulmonary breast cancer metastases (red arrows). The mouse lungs were taken at the 12th post different treatments and the gross appearance of pulmonary nodules was photographed. (G) The pulmonary nodules were manually counted and the average numbers were calculated in different groups. ∗∗p < 0.01 versus control, && p < 0.01 EXO-DVDMS versus Free-DVDMS. Data shown are mean ± S.D. of five batches. (H) H&E stained images of lung sections collected from different treated groups of mice. Bar = 50 μm. (I) Immunohistochemistry detection for MMP-9 level of 4T1 tumors after different treatments. (a) Control, (b) US1 (2 W, 3 min)+US2 (3 W, 3 min), (c) Free-DVDMS (2 mg/kg), (d) EXO-DVDMS (2 mg/kg), (e) Free-DVDMS + US1, (f) EXO-DVDMS + US1, (g) Free-DVDMS + US2, (h) EXO-DVDMS + US2, (i) Free-DVDMS + US1+US2, (j) EXO-DVDMS + US1+US2. The image was reproduced from the article published in Theranostics Journal by Liu, Bai, Wang and Co-workers in the year 2019 [426]. Permission was obtained from the publisher for using the illustration. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)