br Fig In vivo targeting ability and PTT e cacy
Fig. 6. In vivo targeting ability and PTT eﬃcacy of PMDIs. (A) In vivo behavior, fluorescence intensity and imaging of major tissues at 48 h post injection after MDA-MB-231 back tumor-bearing nude mice. (B) In vivo imaging of tumors treated with DINPs and PMDIs at 6 h post injection by confocal laser scanning microscopy. Scale bar: 100 μm. (C) photothermal imaging of tumor photothermal eﬃcacy at 6 h post injection (D) In vivo quantitative analysis of tumor photothermal eﬃcacy at 6 h post injection.
increase at the tumor site in the PMDIs-treated groups at 2 h, 4 h, and 6 h relative to DINPs-treated groups. Based on the analysis of organ distribution, the fluorescence intensity of tumors treated with PMDIs was 6.7-fold higher than those treated with DINPs (Fig. 8B, E), in-dicating the high active targeting ability of PMDIs.
The photothermal ability of PMDIs was higher at 6 h post-injection compared to DINPs (Fig. 8C and D). We then explored the therapeutic eﬃciency and anti-metastasis eﬀect of PMDIs in the orthotopic model. In vivo chemo-photothermal therapy was performed in MDA-MB-231-luc tumor-bearing BALB/c-nu mice following diﬀerent treatments (Fig. 9A). Within 20 d, the volumes of tumors remarkably increased to 997 mm3 and 1222 mm3 from the original 150 mm3 in mice injected with free DOX and saline, respectively. These results indicated that these treatments at the experimental conditions did not cause potential eﬃcacy. For PMDs, free ICG + laser group, DINPs + laser group, PMIs + laser group and the DOX + ICG group, we also did not find significant tumor SCH 58261 and the tumors restored growth and in-creased to approximately 350–600 mm3, suggesting an insuﬃcient hyperpyrexia for ablating tumors. By contrast, PMDIs plus laser irra-diation caused a complete tumor ablation, and the tumors nearly dis-appeared after 20 days of treatment (Fig. 8C). r> Based on in vivo bioluminescence imaging 20 d after orthotopic injection with MDA-MB-231-luc cells, mice injected with free DOX and saline exhibited significant sites of cancer metastases. In mice treated with PMDs, free ICG + laser group, DINPs + laser group, PMIs + laser group or even the combination of DOX and ICG group, significant bioluminescence signals were still recorded, indicating high tumor growth and metastasis. However, PMDIs-based photothermal che-motherapy completely ablated the tumors and showed nearly no me-tastasis, results that are highly consistent with the imaging results for tumors (Fig. 9A and B). In addition, no significant changes in body weight were observed in the PMDIs group (Fig. 9E).
Major organs of mice treated with PMDIs also revealed nearly no metastases according to the H&E staining slices (Fig. 9D). In addition, within 80 d, mice treated with PMDIs had a longer survival period, as 2
out of 5 mice died (Fig. 9C), and the tumors became obviously ablated according to the tumor slices (Fig. 9D). Therefore, PMDIs represent a very eﬀective chemo/photothermal agent for preventing orthotopic cancer metastasis.
In this study, we prepared PM-coated PLGA nanoparticles en-capsulating DOX and ICG. The particles were able to track and clear CTCs from both blood circulation and lymphatic circulation due to the high aﬃnity between P-Selectin of PMs and CD44 receptors in tumor cells. In the three xenograft or orthotopic breast tumor-bearing mice models, DOX and ICG co-loading nanoplatelets not only completely ablated the primary tumor but also eﬀectively inhibited breast cancer metastasis. Our findings provide new insights into the clinical appli-cation of the novel nanoplatelets in the treatment of breast cancer and other tumor metastasis.
All relevant data are available from the authors.
Fig. 7. In vivo antitumor eﬃcacy and evaluation of anti-metastasis in back MDA-MB-231 tumor-bearing nude mice. (A) Images of tumors at 20 d post-administration of Saline, DOX, PMDs, ICG + L, PMIs + L, DOX + ICG + L, PMDIs + L treatments. (B) Tumor growth curves. (C) Mice morbidity-free survival period after diﬀerent treatments (5 mice per group). (D) Photos of India-ink staining of whole lungs and H&E staining of the liver and lung sections harvested after diﬀerent treatments. White arrows indicate the visible metastatic nodules. Yellow and red arrows indicate the lung and liver metastases, respectively. Scale bar: 1 mm. (E) The changes in body weight of mice during diﬀerent treatments. ** p < 0.01 versus the control. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)