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

• Published in: Digestive diseases and sciences 2011-10, Vol.56 (10), p.3005-3013
• Main Authors: Yoon, Soon Man, Myung, Seung-Jae, Kim, In-Wha, Do, Eun-Ju, Ye, Byong Duk, Ryu, Ju Hee, Park, Kyeongsoon, Kim, Kwangmeyung, Kwon, Ick Chan, Kim, Mi Jung, Moon, Dae Hyuk, Yang, Dong-Hoon, Kim, Kyoung Jo, Byeon, Jeong-Sik, Yang, Suk-Kyun, Kim, Jin-Ho
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemically induced; Adenocarcinoma - diagnosis; Adenocarcinoma - drug therapy; Animals; Azoxymethane - adverse effects; Biochemistry; Biological and medical sciences; Cell Line, Tumor; Colon - drug effects; Colon - metabolism; Colon cancer; Colonic Neoplasms - chemically induced; Colonic Neoplasms - diagnosis; Colonic Neoplasms - drug therapy; Diagnosis; Diagnostic Imaging - methods; Disease Models, Animal; Disease Progression; Drug Therapy; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Feeding. Feeding behavior; Fluorescence; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Health aspects; Hepatology; Humans; Immunohistochemistry; Investigations; Male; Matrix Metalloproteinase 7 - metabolism; Matrix Metalloproteinase Inhibitors; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred Strains; Nanoparticles; Oncology; Original Article; Peptides; Prevention; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transplant Surgery; Treatment Outcome; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Xenograft Model Antitumor Assays
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-011-1685-z

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