Fig. 1.
Passive delivery of Aux-PEGy NPs to the fibrotic kidney. (A) UUO in mice is obtained by ligating the left ureter twice with sutures. (B) Distribution of Aux-PEGy NPs in the UUO kidney and contralateral (CL) kidney 24 h postinjection into mice on day 7 post-UUO surgery. %ID = percentage of injected dose. Data are from n = 5 to 6, across one experiment. Statistical significance was evaluated using One-Way ANOVA with Tukey’s post hoc test for multiple comparison. All P values ≤ 0.05 are displayed on the graph. All bars and error bars represent mean ± SD. (C) Schematic illustration of kidney anatomy. Each nephron contains two functional subunits, namely glomerulus and the tubular system. The left Inset shows the flow of systemically injected NPs in the blood vessels that surround kidney tubules (or peritubular capillaries) and the right Inset shows the flow of NPs in the lumen of a renal tubule. (D) Silver enhancement staining of UUO kidney tissues showed that smaller Au2-PEG200 and Au3-PEG500 NPs could be found in the tubule lumen (red arrow), but larger Au5-PEG1000, Au5-PEG5000, and Au20-PEG5000 NPs localized in peritubular capillaries (green arrow). Yellow or black dots: Au2 NPs; black dots: AuNPs of larger sizes. The negative control histological image of the fibrotic kidney from uninjected mice shows the lack of detectable silver signals. Representative images from three kidney sections from each mouse, n = 3 mice/group. Representative locations of the renal tubule and tubule lumen were annotated as “t” and “l”, respectively. (E) Distribution of Au3-PEG500 NPs to the UUO and CL kidneys 24 h postinjection as a function of disease stage. Data are presented in terms of %ID/ g of kidney tissue. Data are from n = 3, across one experiment.