Effect of Size and Targeting Agent on Biodistribution of Polystyrene Nanoparticles in Apolipoprotein E Knock-Out and Wild-Type Mice

<b>Objectives:</b> We investigated the in vivo biodistribution of vascular cell adhesion molecule-1 (VCAM-1)-targeting polystyrene nanoparticles (PS-NPs) labeled with Rhodamine B in a murine model of atherosclerosis. <b>Methods:</b> Targeted PS-NPs of varying sizes were first assessed for in vitro uptake in RAW264.7 cells. In vivo evaluation with VCAM-1-targeted nanoparticles (NP T) in C57 BL/6NtaC mice was conducted, and organs were analyzed 1, 6, and 24 h post injection, ex vivo. Subsequently, both targeted (NP T) and non-targeted (NP NT) nanoparticles of 30, 60, and 120 nm were injected into Apolipoprotein E knock-out (ApoE KO) mice on a high-fat diet, with ex vivo organ analysis 24 h post injection. <b>Results:</b> Results showed that NP30 T and NP60 T accumulated primarily in the liver and kidney of B6 mice. In ApoE KO mice, biodistribution was largely unaffected by size and targeting, except for higher uptake of NP 120 NT and T in the lungs and spleen. All NP types, except NP60 NT, showed significantly higher signal in ApoE KO mouse aortas compared to saline controls, with no significant differences between NP groups. <b>Conclusions:</b> While nanoparticles accumulated significantly in ApoE KO mouse aortas compared to controls, size and targeting properties did not significantly affect biodistribution in major organs 24 h post injection.