Abstract
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.
Highlights
Tumor invasion and metastasis define malignancy, which are the major causes of cancer mortality.Metastasis is a complex multi-step process involving detachment of tumor cells from the primary tumor, invasion through the basement membrane, intravasation into the circulatory system, extravasation at a distant site, and outgrowth of a secondary tumor [1]
We focused on development of a metastatic tumor imaging techniques using nanoparticles that target Matrix metalloproteinase 2 (MMP-2) in cancer cells
Characterization of the Protein Nanocages Modified with CTT Peptides
Summary
Tumor invasion and metastasis define malignancy, which are the major causes of cancer mortality. MMP-2 is a potential target for metastatic tumor imaging. Positron emission tomography of MMP-2 has been performed in a metastatic tumor model in vivo using 64Cu-DOTA-CTT [12]. We focused on development of a metastatic tumor imaging techniques using nanoparticles that target MMP-2 in cancer cells. These nanoparticles were developed by a genetic engineering approach involving the addition of CTT peptides to the exterior surface of the nanoparticle. We determined the physical properties, MMP-2-binding capacity, cytotoxicity, and cellular uptake of CTT peptide-conjugated protein nanocages, and applied them as an NIR fluorescence contrast agent to detect tumor cells in vivo
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