Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 16, Issue 1, Pages 148-158Publisher
MDPI
DOI: 10.3390/ijms16010148
Keywords
matrix metalloproteinase; protein nanocages; CTT peptides; metastatic tumor; in vivo fluorescence imaging
Funding
- Ministry of Health, Labour and Welfare of Japan
- Special Coordination Funds for Promoting Science and Technology (SCF funding program Innovation Center for Medical Redox Navigation)
- Ministry of Education, Culture, Sports, Science and Technology of Japan [24300172, 25750176]
- Grants-in-Aid for Scientific Research [15H03007, 25750176, 26108010, 15K12544, 21103001, 15K16333] Funding Source: KAKEN
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Matrix metalloproteinase 2 (MMP-2) in metastatic cancer tissue, which is associated with a poor prognosis, is a potential target for tumor imaging in vivo. Here, we describe a metastatic cancer cell-targeted protein nanocage. An MMP-2-binding peptide, termed CTT peptide (CTTHWGFTLC), was conjugated to the surface of a naturally occurring heat shock protein nanocage by genetic modification. The engineered protein nanocages showed a binding affinity for MMP-2 and selective uptake in cancer cells that highly expressed MMP-2 in vitro. In near-infrared fluorescence imaging, the nanocages showed specific and significant accumulation in tumor tissue after intravenous injection in vivo. These protein nanocages conjugated with CTT peptide could be potentially applied to a noninvasive near-infrared fluorescence detection method for imaging gelatinase activity in metastatic tumors in vivo.
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