Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy

Hong Yeol Yoon, Heebeom Koo, Ki Young Choi, So Jin Lee, Kwangmeyung Kim, Ick Chan Kwon, James F. Leary, Kinam Park, Soon Hong Yuk, Jae Hyung Park, Kuiwon Choi

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206 Citations (Scopus)

Abstract

Tumor-targeted imaging and therapy have been the challenging issue in the clinical field. Herein, we report tumor-targeting hyaluronic acid nanoparticles (HANPs) as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous photodynamic imaging and therapy. First, self-assembled HANPs were synthesized by chemical conjugation of aminated 5β-cholanic acid, polyethylene glycol (PEG), and black hole quencher3 (BHQ3) to the HA polymers. Second, Ce6 was readily loaded into the HANPs by a simple dialysis method resulting in Ce6-loaded hyaluronic acid nanoparticles (Ce6-HANPs), wherein in the loading efficiency of Ce6 was higher than 80%. The resulting Ce6-HANPs showed stable nano-structure in aqueous condition and rapid uptake into tumor cells. In particular Ce6-HANPs were rapidly degraded by hyaluronidases abundant in cytosol of tumor cells, which may enable intracellular release of Ce6 at the tumor tissue. After an intravenous injection into the tumor-bearing mice, Ce6-HANPs could efficiently reach the tumor tissue via the passive targeting mechanism and specifically enter tumor cells through the receptor-mediated endocytosis based on the interactions between HA of nanoparticles and CD44, the HA receptor on the surface of tumor cells. Upon laser irradiation, Ce6 which was released from the nanoparticles could generate fluorescence and singlet oxygen inside tumor cells, resulting in effective suppression of tumor growth. Overall, it was demonstrated that Ce6-HANPs could be successfully applied to in vivo photodynamic tumor imaging and therapy simultaneously.

Original languageEnglish
Pages (from-to)3980-3989
Number of pages10
JournalBiomaterials
Volume33
Issue number15
DOIs
Publication statusPublished - 2012 May

Keywords

  • Chlorin e6
  • Hyaluronic acid
  • Imaging
  • Nanoparticle
  • Photodynamic therapy
  • Tumor-targeting

ASJC Scopus subject areas

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

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  • Cite this

    Yoon, H. Y., Koo, H., Choi, K. Y., Lee, S. J., Kim, K., Kwon, I. C., Leary, J. F., Park, K., Yuk, S. H., Park, J. H., & Choi, K. (2012). Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy. Biomaterials, 33(15), 3980-3989. https://doi.org/10.1016/j.biomaterials.2012.02.016