Promoting the Delivery of Nanoparticles to Atherosclerotic Plaques by DNA Coating

Abstract

Many nanoparticle-based carriers to atherosclerotic plaques contain peptides, lipoproteins, and sugars, yet the application of DNA-based nanostructures for targeting plaques remains infrequent. In this work, we demonstrate that DNA-coated superparamagnetic iron oxide nanoparticles (DNA-SPIONs), prepared by attaching DNA oligonucleotides to poly(ethylene glycol)-coated SPIONs (PEG-SPIONs), effectively accumulate in the macrophages of atherosclerotic plaques following an intravenous injection into apolipoprotein E knockout (ApoE −/− ) mice. DNA-SPIONs enter RAW 264.7 macrophages faster and more abundantly than PEG-SPIONs. DNA-SPIONs mostly enter RAW 264.7 cells by engaging Class A scavenger receptors (SR -A) and lipid rafts and traffic inside the cell along the endolysosomal pathway. ABS-SPIONs, nanoparticles with a similarly polyanionic surface charge as DNA-SPIONs but bearing abasic oligonucleotides also effectively bind to SR-A and enter RAW 264.7 cells. Near-infrared fluorescence imaging reveals evident localization of DNA-SPIONs in the heart and aorta 30 min postinjection. Aortic iron content for DNA-SPIONs climbs to the peak (∼60% ID/g) 2 h post-injection (accompanied by profuse accumulation in the aortic root), but it takes 8 h for PEG-SPIONs to reach the peak aortic amount (∼44% ID/g). ABS-SPIONs do not appreciably accumulate in the aorta or aortic root, suggesting that the DNA coating (not the surface charge) dictates in vivo plaque accumulation. Flow cytometry analysis reveals more pronounced uptake of DNA-SPIONs by hepatic endothelial cells, splenic macrophages and dendritic cells, and aortic M2 macrophages (the cell type with the highest uptake in the aorta) than PEG-SPIONs. In summary, coating nanoparticles with DNA is an effective strategy of promoting their systemic delivery to atherosclerotic plaques.

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…For instance, poly(maleic anhydride-alt-1-decene)-dimethylamino propylamine (PMAL)-coated IONs decorated with the low molecular weight CPP, protamine, showed enhanced endocytic uptake through proteoglycan-dependent binding. The internalization results were superior than PEI and commercially available Lipofectamine nanoparticles [ 144 ].…”

Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy

“…As we all know, the aorta of the mouse is connected to the heart. In the previously reported articles on targeted nanoparticles targeting to atherosclerotic lesions in vivo, the aorta and heart are often used as target sites [ 27 , 34 , 35 ]. Our results showed that Rap/Fe 3 O 4 @Lipo and Rap/Fe 3 O 4 @VHP-Lipo had significantly different enrichment sites, suggesting that Rap/Fe 3 O 4 @VHP-Lipo would have a targeting effect to atherosclerotic lesion sites in mice.…”

Nanoparticle-Based Approaches towards the Treatment of Atherosclerosis

“…The magnetic composite exhibits excellent anti-atherosclerotic effects by alleviating inflammation and oxidative stress as well as promoting cholesterol efflux via reverse cholesterol transport pathways. Another example of the non-target coating was demonstrated by Zhang et al [158]. The authors demonstrated that DNA-coated PEGylated SPIONs effectively accumulate in the macrophages of atherosclerotic plaques after the intravenous injection into ApoE −/− mice.…”