Sticking to the Problem: Engineering Adhesion in Molecular Endoscopic Imaging.

Cancers of the digestive tract cause nearly one quarter of the cancer deaths worldwide, and nearly half of these are due to cancers of the esophagus and colon. Early detection of cancer significantly increases the rate of survival, and thus it is critical that cancer within these organs is detected early. In this regard, endoscopy is routinely used to screen for transforming/cancerous (i.e. dysplastic to fully cancerous) tissue. Numerous studies have revealed that the biochemistry of the luminal surface of such tissue within the colon and esophagus becomes altered throughout disease progression. Molecular endoscopic imaging (MEI), an emerging technology, seeks to exploit these changes for the early detection of cancer. The general approach for MEI is as follows: the luminal surface of an organ is exposed to molecular ligands, or particulate probes bearing a ligand, cognate to biochemistry unique to pre-cancerous/cancerous tissue. After a wash, the tissue is imaged to determine the presence of the probes. Detection of the probes post-washing suggests pathologic tissue. In the current review we provide a succinct, but extensive, review of ligands and target moieties that could be, or are currently being investigated, as possible cognate chemistries for MEI. This is followed by a review of the biophysics that determines, in large part, the success of a particular MEI design. The work draws an analogy between MEI and the well-advanced field of cell adhesion and provides a road map for engineering MEI to achieve assays that yield highly selective recognition of transforming/cancerous tissue in situ.

An adhesion based approach for the detection of esophageal cancer.

Esophageal cancer has a 5 year survival rate of ∼20%. This dismal prognosis is due, in part, to the fact that esophageal cancer often presents at a late stage. Thus, there is a critical need for assays that enable the early detection of cancerous tissue within the esophagus. The luminal surface of the esophagus expresses signature molecule(s) at sites of transformation providing an avenue for the development of in situ assays that detect neoplastic growth within the esophagus. An attractive approach, receiving increased attention, is the endoscopic administration of particles conjugated with ligands to signature molecules present on transforming tissue. Detection of the particles within the esophagus, post-washing, would indicate the presence of the signature molecule and thus transforming tissue. In this work, we utilized cancerous and normal esophageal cells to provide in vitro proof of principle for this approach utilizing ligand-conjugated microspheres and demonstrate the need, and provide the framework for, engineering this technology. Specifically, the study (i) reveals selective increased expression of signature molecules on cancerous esophageal cells relative to normal cells; (ii) demonstrates selective binding of ligand-conjugated microspheres to cancerous esophageal cells relative to normal cells; (iii) demonstrates that the selective recognition of cancerous, relative to normal esophageal cells, is highly dependent on the biophysical design of the assay; and (iv) advocates utilizing the knowledge from the field of cell adhesion as a guide for the effective development of ligand-conjugated particle-based schemes that seek to detect esophageal oncogenesis in situ.