Application of near-infrared fluorescence imaging using a polymeric nanoparticle-based probe for the diagnosis and therapeutic monitoring of colon cancer

Soon Man Yoon, Seung Jae Myung, In Wha Kim, Eun Ju Do, Byong Duk Ye, Ju Hee Ryu, Kyeongsoon Park, Kwangmeyung Kim, Ick Chan Kwon, Mi Jung Kim, Dae Hyuk Moon, Dong Hoon Yang, Kyoung Jo Kim, Jeong Sik Byeon, Suk Kyun Yang, Jin Ho Kim

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Early and accurate detection of adenomatous colonic polyps is a major concern in the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging with optical probes targeting specific peptides enables the noninvasive visualization and characterization of lesions. Matrix metalloproteinases (MMPs) are known to play an important role in tumorigenesis and tumor progression. Aim: To investigate the effectiveness of NIRF imaging, with a novel MMP-activatable probe based on a polymeric nanoparticle platform, in the colon cancer models. Methods: We used an azoxymethane (AOM)-induced mouse colon cancer model resembling human sporadic colon cancer and an MMP-positive xenograft tumor model. MMP expression was evaluated by Western blotting, real-time PCR, and immunohistochemical staining. NIRF imaging was performed with a novel MMP-activatable probe, an MMP-inactivatable probe, and saline. In addition, we observed the change of NIRF signal intensity after intratumoral administration of an MMP-inhibitor. Results: Multiple tumors with various sizes developed in AOM-treated mouse colons, progressing from adenomas to adenocarcinomas, with MMP expression progressively increasing in the normal-adenoma-adenocarcinoma sequence. In mice injected with the MMP-activatable probe, the NIRF signal also increased in this sequence and was highly correlated with MMP expression (p < 0.001). Tumor-background-ratios (TBR) of adenocarcinoma to adjacent normal mucosa by a novel probe were significantly higher than that of adenoma (p < 0.001). In both the AOM and xenograft models, NIRF signals of tumors decreased after treatment with an MMP-inhibitor. Conclusions: NIRF imaging using a polymeric nanoparticle-based probe may be useful for detecting early stage disease and for assessing treatment response.

Original languageEnglish
Pages (from-to)3005-3013
Number of pages9
JournalDigestive Diseases and Sciences
Volume56
Issue number10
DOIs
Publication statusPublished - 2011 Oct

Keywords

  • Colon cancer
  • Matrix metalloproteinases
  • Nanoparticles
  • Near-infrared fluorescence

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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  • Cite this

    Yoon, S. M., Myung, S. J., Kim, I. W., Do, E. J., Ye, B. D., Ryu, J. H., Park, K., Kim, K., Kwon, I. C., Kim, M. J., Moon, D. H., Yang, D. H., Kim, K. J., Byeon, J. S., Yang, S. K., & Kim, J. H. (2011). Application of near-infrared fluorescence imaging using a polymeric nanoparticle-based probe for the diagnosis and therapeutic monitoring of colon cancer. Digestive Diseases and Sciences, 56(10), 3005-3013. https://doi.org/10.1007/s10620-011-1685-z