Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer

Title
Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer
Authors
윤순만명승재김인화도은주예병덕류주희박경순김광명권익찬김미정문대혁양동훈김경조변정식양석균김진호
Keywords
Colon cancer; Near-infrared fluorescence; Nanoparticles; Matrix metalloproteinases
Issue Date
2011-10
Publisher
Digestive diseases and sciences
Citation
VOL 56, NO 10, 3005-3013
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, realtime 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.
URI
http://pubs.kist.re.kr/handle/201004/40293
ISSN
0163-2116
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KIST Publication > Article
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