Polyethylene glycol-conjugated hyaluronic acid-ceramide self-assembled nanoparticles for targeted delivery of doxorubicin

Hyun Jong Cho, In Soo Yoon, Hong Yeol Yoon, Heebeom Koo, Yu Jin Jin, Seung Hak Ko, Jae Seong Shim, Kwangmeyung Kim, Ick Chan Kwon, Dae Duk Kim

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

Polyethylene glycol (PEG)-conjugated hyaluronic acid-ceramide (HACE) was synthesized for the preparation of doxorubicin (DOX)-loaded HACE-PEG-based nanoparticles, 160 nm in mean diameter with a negative surface charge. Greater uptake of DOX from these HACE-PEG-based nanoparticles was observed in the CD44 receptor highly expressed SCC7 cell line, compared to results from the CD44-negative cell line, NIH3T3. A strong fluorescent signal was detected in the tumor region upon intravenous injection of cyanine 5.5-labeled nanoparticles into the SCC7 tumor xenograft mice; the extended circulation time of the HACE-PEG-based nanoparticle was also observed. Pharmacokinetic study in rats showed a 73.0% reduction of the in vivo clearance of DOX compared to the control group. The antitumor efficacy of the DOX-loaded HACE-PEG-based nanoparticles was also verified in a tumor xenograft mouse model. DOX was efficiently delivered to the tumor site by active targeting via HA and CD44 receptor interaction and by passive targeting due to its small mean diameter (<200 nm). Moreover, PEGylation resulted in prolonged nanoparticle circulation and reduced DOX clearance rate in an in vivo model. These results therefore indicate that PEGylated HACE nanoparticles represent a promising anticancer drug delivery system for cancer diagnosis and therapy.

Original languageEnglish
Pages (from-to)1190-1200
Number of pages11
JournalBiomaterials
Volume33
Issue number4
DOIs
Publication statusPublished - 2012 Feb

Keywords

  • Doxorubicin
  • Hyaluronic acid-ceramide-polyethylene glycol
  • Prolonged circulation
  • Theranostic nanoparticle
  • Tumor-targeting

ASJC Scopus subject areas

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

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  • Cite this

    Cho, H. J., Yoon, I. S., Yoon, H. Y., Koo, H., Jin, Y. J., Ko, S. H., Shim, J. S., Kim, K., Kwon, I. C., & Kim, D. D. (2012). Polyethylene glycol-conjugated hyaluronic acid-ceramide self-assembled nanoparticles for targeted delivery of doxorubicin. Biomaterials, 33(4), 1190-1200. https://doi.org/10.1016/j.biomaterials.2011.10.064