A DNA aptamer recognizing MMP14 for in vivo and in vitro imaging identified by cell-SELEX.

A key challenge for the management of various types of cancer, including pancreatic cancer and hepatocellular carcinoma, is accurate diagnosis at an early stage. Matrix metalloproteinase 14 (MMP14) is overexpressed in numerous types of cancer and is associated with poor prognosis. Therefore, MMP14-specific imaging probes have potential use in the diagnosis of MMP14-positive cancer. Aptamers are short oligonucleotide sequences that can bind to molecular targets with a high specificity and affinity. Aptamers are typically obtained from an library; this process is usually termed systematic evolution of ligands by exponential enrichment (SELEX). In the present study, a DNA aptamer targeting MMP14 was obtained by cell-SELEX and termed M17, which specifically recognizes MMP14-positive cells. Aptamer M17 selectively binds to membrane proteins of MMP14-transfected 293T cells (Kd, 4.98±1.26 nM). Pancreatic cancer cell imaging suggested that aptamer M17 can bind to the cell membranes of two pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). tumor imaging demonstrated that the targeting recognition of MIA PaCa-2 tumor cells in mice could be visualized using Cy5-labeled aptamer M17. Aptamer M17-conjugated polyethylene glycol-Fe3O4 can specifically bind to MIA PaCa-2 and PANC-1 cells, and reduce MRI T2-weighted imaging signal intensity. The DNA aptamer M17 has the advantages of simplicity of synthesis, small size, low immunogenicity, high penetrability and high affinity. Therefore, aptamer M17 is a potential molecular probe for the diagnosis and treatment of MMP14-positive cancer.