Peanut Agglutinin-Immobilized Fluorescent Nanospheres with Surface Poly(N-vinylacetamide) Chains as a Novel Colonoscopic Imaging Agent

Abstract

AbstractA goal of our research is to develop a colonoscopic imaging agent that enables real-time and accurate diagnosis of small-sized colorectal cancer. Colorectal cancer first develops in the mucous membrane of the large intestine. We designed an imaging agent that can recognize tumor-derived changes on the mucosal side of epithelial cells in the large intestine with high affinity and specificity. The agent is peanut agglutinin (PNA)-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) (PNVA) chains encapsulating coumarin 6. PNA is a targeting moiety that binds to β-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which is the terminal sugar of the Thomsen-Friedenreich antigen that is specifically expressed on the mucosal side of colorectal cancer cells. The tumor-derived change in the large intestinal mucosa is very small throughout the entire large intestine. To detect such a small change accurately, the imaging agent should have a strong affinity for targets with minimal nonspecific interactions with nontargets. PNVA is also immobilized on the nanosphere surface to enhance the specificity of PNA by reducing the nonspecific interactions between the imaging agent and normal tissues. Coumarin 6 is used as the fluorescent dye that provides an endoscopically detectable fluorescence intensity. It is anticipated that intracolonic (enema) administration of the imaging agent leads to the specific accumulation on the mucosal surface of tumor tissues in the large intestine with resulting fluorescence. Real-time and accurate diagnosis of small-sized early colorectal cancer can be then achieved through observations of a clear fluorescence contrast between the normal and tumor tissues using the standard fluorescence endoscopy.KeywordsEndoscopic imaging agentColonoscopyColorectal cancerPeanut agglutininPoly(N-vinylacetamide)