Figure 3.

Mouse dorsal skin-fold window chamber made of two symmetrical titanium frames. A tumor xenograft was inoculated into a nu/nu mouse window chamber (A). After implanting the MDA-231 breast cancer tumor xenograft, tumor blood vessels were observed to be growing in the window chamber on d 1 (B) and d 15 (C). Normal blood vessel images after iv injection of DOX-loaded pH-sensitive micelles 5 min and 60 min are shown in (D) and (E), respectively. The tumor blood vessels after iv injection of DOX-loaded pH-insensitive and pH-sensitive micelles at the time course for 60 min are presented in (F) and (G) rows. The tight junctions between cells in the endothelial lining of blood vessels in normal tissues do not allow the drug-loaded micelles (indicated by cross) to enter into the tissues. In contrast, tumors are characterized by defective vasculature with large gaps between the endothelial cells, which allowed the drug-loaded micelles enter into the gaps, causing their accumulation in the tumor interstitium.