| Resumo: |
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. |