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. Author manuscript; available in PMC: 2022 Jan 1.
Published in final edited form as: Biomaterials. 2020 Nov 23;268:120528. doi: 10.1016/j.biomaterials.2020.120528

Figure 1. PAFR inhibitor ABT-491 rescues acute toxicities associated with high-dose si-NP injection.

Figure 1.

A) Upon intravenous injection of si-NPs at high N:P ratio (high polymer dose) and 1.2 mg/kg siRNA, 4 out of 5 mice experienced fatalities within 1 hour, but mortality was fully prevented by pre-injection of ABT-491 10 minutes prior to injection of the same si-NP dose (n=5 mice per group). B) Gross pathology demonstrates vasodilatory pathology in major blood vessels (yellow arrows) and reddening of intestines (black arrows, circles) in mice treated with si-NPs. C-E) Mice injected with high-dose si-NPs experienced significant increases in blood hematocrit (C), hemoglobin (D), and red blood cell concentration (E), all of which were abrogated by ABT-491 pretreatment. F) Pancreas wet weight vs. dry weight with 1.2 mg/kg si-NPs (n=5–7), saline, or si-NPs with ABT-491 pre-treatment. G) Evans Blue concentration (as a marker for vascular leakiness) in mouse livers. H) Duodenum hemoglobin concentration (n=5–7, * p<0.05, ** p<0.01, *** p<0.001). I) H&E staining of mouse liver, kidney, and spleen after i.v. injection demonstrating red blood cell congestion in each tissue. Scale bars = 100 μm. All measures were made 30 minutes after injection.