Nanoparticle-Enhanced molecular Fluorescence-Endoscopy for detection of colon cancer (NanoEFEct)

It is the aim of this Project to develop, design and realize a multidimensional data evaluation system optimized for step-by-step approach for accompanying and facilitating the development of nanoparticles as an in-vivo diagnostic tool for the detection of precancerous and early cancerous lesions in the colon via fluoroscopy. Each nanoparticle (NP) will contain (1) the nanoparticle itself based on albumin, gold or biodegradable polymers, (2) the EpCAM antibody and (3) a licensed fluorochrome such as IndoCyanin Green (ICG). Regulatory guidance will already be applied to choose the right starting materials like the use of certain versions of the tagging and targeting groups. The project will collect, evaluate and cross-check all data, like data on physicochemical characteristics, targeting properties of EpCAM-targeted NPs in vitro, fluorescence optical properties of fluorophore-tagged NPs in vitro, NP stability in body fluids at body temperature in vitro, NP stability in conditions relevant to shelf life and transport in vitro, cytotoxicological characteristics of NPs. Based on these data, it will be decided together with the international partners which NPs can proceed to the next step or need further improvement. The Project will apply a similar strategy for in vivo testing on human biopsates and animal models for testing the applicability in a mouse colonoscopy model. During the Project`s lifetime, the Project will be continuously evaluated from a regulatory perspective, and new regulatory guidance will be reviewed for applicability; we will actively foster communication with and seek advice from European and National Regulatory Authorities. Contacts with regulators will be largely informal, but the Project also aims to apply for Scientific Advice at the National Regulatory Authority in Austria (AGES) and to implement the advice received in order to meet the goal to provide Nanoparticle-enhanced fluoro- chromo-endoscopic molecular imaging systems adapted for routine clinical applications, and conforming to safety and efficacy criteria to find best suitable candidate(s) for further development as an in-vivo diagnostic tool and enabling the start of clinical trials.

Our Project developed a new method for the early detection of colon cancer, based on the use of nanoparticles during cancer screening. Colon cancer is one of the commonest cancers, worldwide there are about 1.4 million new cases per year. It has a high death rate, largely due to the difficulty of diagnosing the early stages: even in the carefully cleaned gut wall it is not always possible to recognize the cancer cells with certainty. At this point our project makes its contribution: in our concept, with the help of nanoparticles the cancer cells are made to light up brightly, making them much easier to detect, which aids the diagnosis. During the endoscopic examination of the colon, spraying the nanoparticles onto suspicious sites in the gut wall causes a bright image to appear at malignant sites when these are illuminated by a special light, thus signaling the presence of cancer. Our projects Principle Investigator was the Coordinator in the European Unions international translational cancer research consortial project NanoEFEct. Three members of the NanoEFEct consortium, including our Innsbruck team and partners in Trondheim (Norway) and Porto (Portugal), created different types of nanoparticles and tested one anothers products. Our fourth member in Erlangen (Germany) was a clinical partner, at the university clinic of gastroenterology, and tested the nanoparticles produced by the three nanoparticle laboratories in studies of cancer cells and of mice bearing colon cancers. Our fifth partner was CESAR (Vienna), an Austrian management team with experience in coordinating clinical research. All three scientific partners created nanoparticles that fulfill the aim of lighting up colon cancers, both in human materials and in mouse research models. This consortial research result proved conclusively that our aim is feasible, that our concept of aiding diagnosis by generating a bright image of each tumour in the colon wall is proven to work. Our successful concept functions in the laboratory and now needs to be developed for use in clinics. In further work we will study the advantages and disadvantages of each of the three different nanoparticle versions, in order to identify the most effective version and the safest version. In this project, we aimed to create knowledge useful in developing products for clinical use in colon cancer. Our diagnostic procedure can however be adapted easily for use in the diagnosis of other types of cancer, such as for example lung cancers, ear-nose-throat cancers, and genito-urinary cancers. The social and economic impact of our work is therefore potentially extremely large. In future work we will focus on developing safe and effective nanoparticles for use in diagnosis of several other major diseases.