CD47-targeted nano-immunotherapy for treatment of atherosclerosis

In this ongoing project funded by the American Heart Association, we pursued the development of targeted nanotherapeutics to inhibit the CD47/SIRPα immune checkpoint axis, a promising strategy for enhancing macrophage-mediated clearance of diseased tissue in atherosclerosis. We evaluated multiple nanoparticle and small-molecule combinations, ultimately selecting a ferumoxytol (FMX) nanoparticle loaded with the potent CD47 downregulator RRx-001 emerged as the lead nanotherapeutic candidate. In vitro and in vivo imaging studies demonstrated that FMX nanoparticles preferentially accumulate in macrophage-rich regions of atherosclerotic plaques. Using fluorescently labeled FMX in ApoE−/− mice, we showed selective deposition of nanoparticles in inflamed aortic lesions. Fluorescence microscopy revealed colocalization of FMX with macrophages (MAC-3+), confirming their cellular targeting specificity. Quantitative analysis indicated significantly greater FMX uptake by macrophages compared to endo..., , # CD47-targeted nano-immunotherapy for treatment of atherosclerosis

Dataset DOI: [10.5061/dryad.05qfttffw](10.5061/dryad.05qfttffw)

This preliminary data report describes the development of targeted nanotherapeutics to inhibit the CD47/SIRPα immune checkpoint and enhance macrophage-mediated clearance in atherosclerosis. Ferumoxytol (FMX) nanoparticles loaded with the CD47 downregulator RRx-001 showed preferential accumulation in macrophage-rich regions of atherosclerotic plaques in vitro and in vivo. Imaging and quantitative analysis confirmed selective uptake by macrophages compared to other vascular cell types. Preliminary efficacy studies in ApoE−/− mice suggest that FMX-CD47 formulations may reduce plaque formation.

## Description of the data and file structure

**Figure_1.jpg description:**

**Fig. 1 A, B:** Design and synthesize small-molecule inhibitors targeting the CD47/SIRPα axis.

As shown in the figure, ferumoxytol (FMX) was chosen as the platform for drug loading. FMX wa...,