title: Hyaluronic acid nanoparticles for active targeting atherosclerosis.
abstract: For the effective diagnosis and therapy of atherosclerosis, there is a pressing need to develop the carrier which can specifically deliver the agents to the pathological site. Since the representative hallmark of atherosclerosis in its pathogenic process is the over-expression of the receptors for hyaluronic acid (HA) such as stabilin-2 and CD44, we herein investigated the potential of HA nanoparticles (HA-NPs) as the carrier for active targeting atherosclerosis. From in vitro cellular uptake tests, it was revealed that HA-NPs were selectively taken up by the cells over-expressing stabilin-2 or CD44. On the other hand, the cellular uptake of HA-NPs was drastically reduced when the cells were pre-treated with excess amount of free HA, implying that HA-NPs were taken up by the receptor-mediated endocytosis. Following systemic administration of Cy5.5-labeled NPs into the ApoE-deficient mice as the animal model, the atherosclerotic legion was assessed at 24 post-injection by using the optical imaging system. Interestingly, the fluorescent signal of the atherosclerotic lesion by HA-NPs was much stronger than that of the normal aorta. Three dimensional z-stack images of an atherosclerotic plaque indicated the even distribution of HA-NPs in the atherosclerotic legion. It was demonstrated by immunohistochemistry that HA-NPs were co-localized with the HA receptors including stabilin-2 and CD44. In addition, the amount of HA-NPs, accumulated in the atherosclerotic lesion, was much higher than that of HGC-NPs, known to reach the atherosclerotic lesion by the passive targeting mechanism. Overall, it was evident that HA-NPs could effectively reach the atherosclerotic lesion via the active targeting mechanism after systemic administration, implying their high potential as the carrier for diagnosis and therapy of atherosclerosis.
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea; Division of High-risk Pathogen Research, Korea National Institute of Health, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Gyeonggi-do 440-746, Republic of Korea. Electronic address: jhpark1@skku.edu.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; KU-KIST School, Korea University, 1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea. Electronic address: iskim@knu.ac.kr.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000628:therapy*; D002460:Cell Line; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles
chemical_list: D006820:Hyaluronic Acid
keywords: Active targeting; Atherosclerosis; Hyaluronic acid; Nanoparticles