Hyaluronic acid nanoparticles for active targeting atherosclerosis

Ga Young Lee, Jong Ho Kim, Ki Young Choi, Hong Yeol Yoon, Kwang Meyung Kim, Ick Chan Kwon, Kuiwon Choi, Byung Heon Lee, Jae Hyung Park, In-San Kim

Research output: Contribution to journalArticle

50 Citations (Scopus)

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 invitro 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.

Original languageEnglish
Pages (from-to)341-348
Number of pages8
JournalBiomaterials
Volume53
DOIs
Publication statusPublished - 2015 Jun 1

Keywords

  • Active targeting
  • Atherosclerosis
  • Hyaluronic acid
  • Nanoparticles

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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  • Cite this

    Lee, G. Y., Kim, J. H., Choi, K. Y., Yoon, H. Y., Kim, K. M., Kwon, I. C., Choi, K., Lee, B. H., Park, J. H., & Kim, I-S. (2015). Hyaluronic acid nanoparticles for active targeting atherosclerosis. Biomaterials, 53, 341-348. https://doi.org/10.1016/j.biomaterials.2015.02.089