Figure 6.
Induction of HSR upon heating in tumor and normal vasculature. (a) Schematic of HGL transgenic model. Heat-responsive promoter elements from the HSPA6 gene regulate expression of GFP-firefly luciferase fusion protein, permitting visualization of the HSR in the host-derived tumor stroma including the neovascular endothelium. (b) Elevated GFP expression following PEG-NR heating in tumors indicates robust induction of the HSR. Tumor vasculature highlighted by intravenous TR-Dextran (TR-Dex). Intrinsic luminescence of PEG-NRs allows for direct detection of nanoparticles by multiphoton microscopy. (c-d) Intravital imaging reveals induction of normal endothelial HSR. Line histogram profiles of normalized GFP and TR-Dex fluorescence intensities at regularly-spaced intervals along vessel after heat exposure (n = 6 equidistant positions along vessel). Scale bar: 50 μm