Figure 1.

ICLs exhibit enhanced extravasation in syngeneic solid tumors. (A) EPC/DSPE-PEG2000/DiI/Cy5-DSPE liposomes were used (Table 1). (B) both dyes are colocalized in liposomes. The size estimate by fluorescence microscopy is not accurate, and readers are referred to Table 1 for accurate size and PDI measurements. (C) Confocal microscopy imaging of fresh 4T1 tumor slices shows colocalization of DiI and Cy5-DSPE in tumor vasculature but predominant extravasation and spreading of DiI at 24 h. (D) Line profiles drawn across representative lectin-labeled tumor blood vessels (Figure S1) show spreading of DiI at 24 h and mostly vascular localization of Cy5-DSPE. (E) Quantification of fluorescence positive areas in the tumor (n = 30–60 images from 2 tumors per time point, paired t test, repeated twice). (F)EPC/DSPE-PEG2000/DiI/Cy5-DSPE liposomes were injected in GL261 syngeneic intracranial glioma bearing mice. Confocal microscopy imaging of brain slices shows predominant extravasation and spreading of DiI, and an almost complete absence of Cy5-DSPE. The tumor (left of dotted boundary as identified by highly irregular tumor blood vessels) is surrounded by normal brain tissue with defined vasculature. (G) Quantification of fluorescence-positive areas in the glioma images (n = 40 images from 2 tumors, paired t test).