Figure 6.

Integrin αvβ3-targeted nanotherapy attenuates breast cancer bone metastases. Following the schematic described in Fig. 5D, mice were treated with either a cumulative dose of 5.55 mg/kg docetaxel (DTX), an equimolar dose of docetaxel-prodrug encapsulated by αvβ3-MP (αvβ3-MP/DTX-PD), or saline. Analyses completed on samples collected on day 12 post-injection. (A) Representative in vivo BLI of mice bearing PyMT-Bo1 bone metastases, matching day 3 and day 12 post-injected mice from each group (B) Ex vivo PyMT-Bo1 bone metastatic tumor burden by BLI analysis, n=9. (C) Histological analysis of tumor burden within the tibiofemoral joint, n=4. (D) X-ray analysis of osteolytic bone destruction, n=9. (B-D) Scale=1 mm, two-tailed unpaired t-test with Bonferroni correction for a priori multiple comparisons between saline and each experimental treatment, * P<(0.05/2). (E) Serum chemistry analysis of BUN, AST, and ALT, n=5. Gray range illustrates the normal reference range (mean±2*SD) for female C57BL/6 mice bearing PyMT-Bo1 metastases. (F) TRAP staining for quantification of osteoclast number per millimeter of bone surface (N.OC/mmB.S.) at the tumor (T), bone (B) interface, n=4. (G) Quantification of PCNA-positive cells within the bone metastatic region, n=3. (F-G) Scale=50 μm, one-way ANOVA with Tukey’s post-hoc test, ** P<0.01, * P<0.05, ns=(not significant). All images are representative and data presented as mean±SEM.