Abstract

Intestinal tumors exhibit cell surface properties that differ from neighboring healthy epithelia and thus allow tumor cellspecific molecular targeting. Ganglioside GM1 is such a discriminatory target. Although expressed in the apical membrane of all intestinal epithelial cells it is accessible for particle conjugated ligands on tumor cells only. In order to exploit this phenomenon we want to develop a nanoparticulate optical contrast agent equipped with a peptidic GM1 binding ligand. For identification of ligand peptides a novel screening platform was devised where potential ganglioside GM1-binding peptides are generated on glass capillary plates using microfluidic non-contact arraying techniques and screened in situ for binding of fluorophor-labeled GM1. These three-dimensional supports are easy to handle and show better sensitivity than either flat glass or membrane supports because of their large inner surface and low interference with readout systems. A custom fluorescence reader was designed to comply with the specific optical behaviour of peptide arrays synthesized on microcapillary plates. This reader uses a small numerical aperture for excitation and a large numerical aperture for detection in epifluorescence-mode. Background noise from fluorescence and Raman scattering is reduced by time gated photon counting. Peptides showing affinity to ganglioside GM1 will be conjugated to a nanoparticulate carrier bearing a fluorescent dye. The resulting optical contrast agent shall be used for fluorescence endoscopic intestinal tumor screening.

© 2007 SPIE