Targeted nanocarriers effectively remove cholesterol from macrophages

BackgroundMacrophages phagocytose large amounts of cholesterol to form foam cells that can aggravate inflammation and further promote the development of atherosclerotic plaque.ObjectiveTo develop novel nanocarriers targeting atherosclerosis-associated macrophages.MethodsCD-G5 was obtained by modifying β-CD onto PAMAM G5.0, and subsequently PEG2000 was used as a linker arm to modify mannose onto PAMAM G5.0 of CD-G5 to obtain CD-G5-PEG-Man. CD-G5-PEG-Man was structurally characterized and evaluated in vitro for its cell biological functions.ResultsCD-G5-PEG-Man had an average particle size of 110 nm and a regular spherical morphology. CD-G5-PEG-Man showed no significant toxicity to macrophages at all the experimental concentration gradients. Macrophages showed stronger uptake of the fluorescently labelled nanoparticle CD-G5-PEG-Man-FITC than CD-G5-FITC, and the fluorescence weakened with increasing free mannose. Intracellular BODIY-cholesterol fluorescence intensity was weaker in the 200 nM CD-G5-PEG-Man treatment group than in the 100 µM HP-β-CD, 100 nM CD-G5-PEG-Man, and DMSO treatment groups. The higher the amount of β-CD on the CD-G5-PEG-Man, the lower the fluorescence intensity of intracellular BODIY-cholesterol.ConclusionA biosafety nanocarrier, CD-G5-PEG-Man, was successfully developed, in which mannose specifically targets macrophages via mannose receptors on macrophages, and β-CD synergistically promotes cholesterol efflux from macrophages.