Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer
- Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer
- 윤순만; 명승재; 김인화; 도은주; 예병덕; 류주희; 박경순; 김광명; 권익찬; 김미정; 문대혁; 양동훈; 김경조; 변정식; 양석균; 김진호
- Colon cancer; Near-infrared fluorescence; Nanoparticles; Matrix metalloproteinases
- Issue Date
- Digestive diseases and sciences
- VOL 56, NO 10, 3005-3013
- 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.
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