Abstract
Control of colorectal carcinoma (CRC) is hindered because early cancerous lesions in the colorectal wall may not be visible at colonoscopy, a screening technique allowing diagnosis and immediate resection of CRC. Colonoscopy misses 6% of all CRCs and 12-17% of adenomas larger than 1 cm. To improve detection of early-stage CRC, we propose nanoparticle-enhanced fluorescence endoscopy. The consortium of 5 partners includes three leading teams developing biodegradable nanoparticles for molecular imaging, a leading team working clinically and scientifically with fluorescence endoscopy in patients and in mouse models, and a team of scientists and clinicians widely experienced in the complex regulatory, legal and ethical issues associated with nanomedicine and with translational work bringing pharmaceutical products into clinical use. Targeting groups attached to the nanoparticles will bind them securely and specifically to EpCAM proteins heavily upregulated on ~ 98% of CRC cell surfaces, analogously to the binding underlying the licensed antibody therapy using Catumaxomab. Fluorescent tags on the nanoparticles will allow contrasty imaging in a fluorescence endoscope. Closely cooperating with surgeons and pathologists, we will prepare diagnostically relevant nanoparticles by GMP, ready for rapid translational development towards preclinical testing at the end of the project. Ethical and regulatory issues are addressed from the beginning, so input from appropriate advisors (e.g. the Austrian regulatory agency AGES) can guide the research direction from the start.
Final summary
Colon cancer affects ~ 6 % of the population and is the second leading cause of cancer related death in Europe and the USA, largely because the disease is not detected early enough. Our project NanoEFEct has developed nanoparticles to help doctors make this early diagnosis. The nanoparticles are designed to help recognise the early tumours by lighting them up. Some of our project partners are doctors, others are chemists, biologists and pharmacists, and one is a medical management partner. We have developed several promising nanoparticle versions and we need to select the best of these and begin preparing them for use in the clinic. Our international European project combines many skills from laboratories, clinics and management centres throughout the European Union. We are as many women as men and our project trains young scientists in new areas of expertise, that is: it provides an interdisciplinary training.
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