Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy

Ki Young Choi, Hong Yeol Yoon, Jong Ho Kim, Sang Mun Bae, Rang Woon Park, Young Mo Kang, In San Kim, Ick Chan Kwon, Kuiwon Choi, Seo Young Jeong, Kwangmeyung Kim, Jae Hyung Park

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283 Citations (Scopus)

Abstract

Tumor targetability and site-specific drug release of therapeutic nanoparticles are key factors for effective cancer therapy. In this study, poly(ethylene glycol) (PEG)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) were investigated as carriers for anticancer drugs including doxorubicin and camptothecin (CPT). P-HA-NPs were internalized into cancer cells (SCC7 and MDA-MB-231) via receptor-mediated endocytosis, but were rarely taken up by normal fibroblasts (NIH-3T3). During in vitro drug release tests, P-HA-NPs rapidly released drugs when incubated with cancer cells, extracts of tumor tissues, or the enzyme Hyal-1, which is abundant in the intracellular compartments of cancer cells. CPT-loaded P-HA-NPs (CPT-P-HA-NPs) showed dose-dependent cytotoxicity to cancer cells (MDA-MB-231, SCC7, and HCT 116) and significantly lower cytotoxicity against normal fibroblasts (NIH-3T3) than free CPT. Unexpectedly, high concentrations of CPT-P-HA-NPs demonstrated greater cytotoxicity to cancer cells than free CPT. An in vivo biodistribution study indicated that P-HA-NPs selectively accumulated into tumor sites after systemic administration into tumor-bearing mice, primarily due to prolonged circulation in the blood and binding to a receptor (CD44) that was overexpressed on the cancer cells. In addition, when CPT-P-HA-NPs were systemically administrated into tumor-bearing mice, we saw no significant increases in tumor size for at least 35 days, implying high antitumor activity. Overall, P-HA-NPs showed promising potential as a drug carrier for cancer therapy.

Original languageEnglish
Pages (from-to)8591-8599
Number of pages9
JournalACS Nano
Volume5
Issue number11
DOIs
Publication statusPublished - 2011 Nov 22

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Keywords

  • Hyal-1
  • camptothecin
  • drug release
  • hyaluronic acid
  • nanoparticle
  • tumor targeting

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Choi, K. Y., Yoon, H. Y., Kim, J. H., Bae, S. M., Park, R. W., Kang, Y. M., Kim, I. S., Kwon, I. C., Choi, K., Jeong, S. Y., Kim, K., & Park, J. H. (2011). Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy. ACS Nano, 5(11), 8591-8599. https://doi.org/10.1021/nn202070n