Figure 6. αMSH-PEG-C′ dots inhibit tumor growth in 786-O and HT-1080 xenograft models.

a,b, Graphical summary of 786-O (a) and HT-1080 (b) average tumor volume measurements in αMSH-PEG-C′ dot-treated (‘particles’; n=5) and control (‘saline-vehicle; n=3) mice; error bars indicate standard deviation. Three, high-dose (12 nanomoles (nmol)/dose) αMSH-PEG-C′ dot or saline vehicle control treatments (30 micromoles/dose) were i.v.-injected (arrows) over a 10-day period, with particle-treated tumours, on average, demonstrating growth inhibition, greater for HT-1080, relative to saline-treated controls. c, Individual HT-1080 tumor volume measurements from part (b) are shown for particle-treated (‘T’) versus saline-treated (‘C’) mice. Relative to control tumor volumes, data show marked inhibition of tumor growth and partial tumor regression after particle treatments (HT-1080: p<0.001; 786-OL P<0.01). P-values are from a Wald test in a regression model estimated by generalized estimating equations to take into account the longitudinal nature of the data. d, Left image: whole body Cy5 fluorescent imaging of a representative H1080 tumor xenograft (arrows). Right image: low-power view of H&E-stained tissue sections from representative control (top) and treated (bottom) tumors reveal a densely cellular and invasive neoplasm exhibiting multifocal necrosis. Control specimens are noted to be disproportionately larger in size than the corresponding treated ones without evident morphological differences. e–h, Immunohistochemical staining of tumor sections with macrophage marker, Mac-2, shows scattered macrophages (arrow) surrounding control tumor sections (T) on (e) low and (g) high power views, while corresponding (f) low and (h) high power views of Mac-2 stained treated sections show large numbers of Mac-2 positive cells circumscribing the tumor at similar locations (boxes, d, f; arrows). Small numbers of intratumoral Mac-2 positive cells are also noted. i, Graphical summary of individual HT-1080 tumor volume measurements in mice undergoing combined inhibitor (Liproxstatin-1) and particle treatment (T+L; n=3) versus particle treatment alone (T; n=3). Three high-dose (12 nmol/dose) αMSH-PEG-C′ dot treatments (with and without i.p.-injected Liproxstatin-1) were given over a 10-day period. Relative to particle treatment alone, marked progression of tumor growth is seen following combined inhibitor and particle treatment (p<0.001). Image: Representative particle-exposed tumors reveal specimens to be disproportionately larger in size when additionally treated with Liproxstatin-1 (right tumor). Scale bars: 1 mm (d, e, and f); 50 μm (g, h); 1 cm (j).