Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer

Ki Young Choi, Eun Jung Jeon, Hong Yeol Yoon, Beom Suk Lee, Jin Hee Na, Kyung Hyun Min, Sang Yoon Kim, Seung Jae Myung, Seulki Lee, Xiaoyuan Chen, Ick Chan Kwon, Kuiwon Choi, Seo Young Jeong, Kwangmeyung Kim, Jae Hyung Park

Research output: Contribution to journalArticle

Abstract

Colon cancer is the second leading cause of cancer-related death in the United States. The considerable mortality from colon cancer is due to metastasis to other organs, mainly the liver. In the management of colon cancer, early detection and targeted therapy are crucial. In this study, we aimed to establish a versatile theranostic system for early tumor detection and targeted tumor therapy by using poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) which can selectively accumulate in tumor tissue. For the diagnostic application, a near-infrared fluorescence (NIRF) imaging dye (Cy 5.5) was chemically conjugated onto the HA backbone of P-HA-NPs. After intravenous injection of Cy5.5-P-HA-NPs into the tumor-bearing mice, small-sized colon tumors as well as liver-implanted colon tumors were effectively visualized using the NIRF imaging technique. For targeted therapy, we physically encapsulated the anticancer drug, irinotecan (IRT), into the hydrophobic cores of P-HA-NPs. Owing to their notable tumor targeting capability, IRT-P-HA-NPs exhibited an excellent antitumor activity while showing a reduction in undesirable systemic toxicity. Importantly, we demonstrated the theranostic application using Cy5.5-P-HA-NPs and IRT-P-HA-NPs in orthotopic colon cancer models. Following the systemic administration of Cy5.5-P-HA-NPs, neoplasia was clearly visualized, and the tumor growth was effectively suppressed by intravenous injection of IRT-P-HA-NPs. It should be emphasized that the therapeutic responses could be simultaneously monitored by Cy5.5-P-HA-NPs. Our results suggest that P-HA-NPs can be used as a versatile theranostic system for the early detection, targeted therapy, and therapeutic monitoring of colon cancer.

Original languageEnglish (US)
Pages (from-to)6186-6193
Number of pages8
JournalBiomaterials
Volume33
Issue number26
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Keywords

  • Colon cancer
  • Hyaluronic acid
  • Irinotecan
  • Nanoparticle
  • Theranostics
  • Tumor targeting

ASJC Scopus subject areas

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

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  • Cite this

    Choi, K. Y., Jeon, E. J., Yoon, H. Y., Lee, B. S., Na, J. H., Min, K. H., Kim, S. Y., Myung, S. J., Lee, S., Chen, X., Kwon, I. C., Choi, K., Jeong, S. Y., Kim, K., & Park, J. H. (2012). Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer. Biomaterials, 33(26), 6186-6193. https://doi.org/10.1016/j.biomaterials.2012.05.029