2009
DOI: 10.1073/pnas.0903369106
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Targeting atherosclerosis by using modular, multifunctional micelles

Abstract: Subtle clotting that occurs on the luminal surface of atherosclerotic plaques presents a novel target for nanoparticle-based diagnostics and therapeutics. We have developed modular multifunctional micelles that contain a targeting element, a fluorophore, and, when desired, a drug component in the same particle. Targeting atherosclerotic plaques in ApoE-null mice fed a high-fat diet was accomplished with the pentapeptide cysteine-arginine-glutamic acid-lysine-alanine, which binds to clotted plasma proteins. The… Show more

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Cited by 257 publications
(262 citation statements)
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“…In comparison, the accumulation of untargeted NWs was low and limited to the luminal surface of plaques. CREKA-targeted NWs showed greater accumulation on the surface of the plaques, and minimally penetrated into the plaques, confirming reported results (10). Ex vivo MRI of aortas from mice injected with LyP-1-NWs revealed decreased T2*-weighted signal in areas that contained plaque (Fig.…”
Section: Resultssupporting
confidence: 75%
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“…In comparison, the accumulation of untargeted NWs was low and limited to the luminal surface of plaques. CREKA-targeted NWs showed greater accumulation on the surface of the plaques, and minimally penetrated into the plaques, confirming reported results (10). Ex vivo MRI of aortas from mice injected with LyP-1-NWs revealed decreased T2*-weighted signal in areas that contained plaque (Fig.…”
Section: Resultssupporting
confidence: 75%
“…Staining with an antifluorescein antibody confirmed the presence of LyP-1 in the plaques. For comparison, we also injected mice with a peptide previously shown to home to plaques, CREKA (10). In agreement with the reported results, FAM-CREKA homed to the plaques in a pattern distinct from LyP-1 in that CREKA was essentially confined to the surface of the plaques (Fig.…”
Section: Resultssupporting
confidence: 73%
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“…They have been shown capable of delivering biologically active peptides for a variety of applications including angiogenesis (19,20), osteogenesis (21,22), neurogenesis (23,24), atherosclerosis treatment (25), cancer therapy (26,27), and islet transplantation (28,29). Also, peptide amphiphile micelles are comprised of a high concentration of peptide (30), inhibit peptide degradation (31), and can greatly increase peptide intracellular delivery (32).…”
Section: Introductionmentioning
confidence: 99%