Colorectal cancer (CC) is widespread and is responsible for many cancer-related deaths. Despite different efforts and great advances in the therapeutic field, 5-year survival for this type of cancer still reaches 65.9% and is conditioned by the stage of disease. Therefore, early diagnosis would represent a significant step forward to improve survival rates and chances of cure. It is now well accepted that nanoparticles (particles with size between 1 and 100 nm) in contact with biological fluids are quickly surrounded by a selected group of adsorbed proteins that form a protein corona whose composition is strongly dependent on the physicochemical properties of the nanoparticles themselves. The protein pattern in cancer patients' blood differs from that of healthy subjects. Thus, the molecular composition of the protein corona formed around nanoparticles does change in cancer and non-cancer patients blood. Characterization of protein corona could therefore allow detection of minor changes in protein concentration at the very early stages of disease development, i.e. when alterations in the circulating levels of proteins are undetectable by blood tests. The main aim of this project is the ultimate development of a disruptive nanoparticle-enabled blood test for early CC detection based on the differences between the protein coronas formed on different types of nanoparticles after exposure to the blood of CC cancer patients and non-cancer subjects. To achieve this, a review of available analytical techniques for nanoparticle characterization and detection of proteins, as well as microfluidics and sensor array technology will be performed. The test will be safe, inexpensive, fast and easy to perform. Due to this unique characteristics, we envision the test will find widespread application in the clinics. Finally, an integrated platform to perform the nanoparticle-enabled blood test will be developed and patented.
Proposed integration with other Early Detection protocol modalities.
To date, there is a lack of effective, minimally invasive tools allowing large-scale screening of CC. On the other side, the emerging PC technology depends on non-invasive and cheap tools. As a consequence, we envision that the NEB test will be used in clinical practice at first level of investigation before taking an action (either to undergo furthermore invasive and expensive investigations or not undergo). Furthermore, discovery of new biomarkers of CC by PC technology, will allow increasing the sensitivity and specificity of routinely analyses. It is known that changes in concentration of blood proteins appear from months to years before diagnosis of cancer and have been discovered in several cancer types. In this regards, the nanoparticle-PC technology offers new exciting opportunities because PC works as a "nano- concentrator" and its specificity derives from the pattern of response among an array of cross-reactive sensors (the 'corona proteins') rather than from individual sensors for specific (bio)molecules. This means that the technology allows detecting changes in the PC even when the total quantity of single protein biomarkers is about the same for cancer and noncancer patients. In addition, we will establish a correlation between test's prediction ability and the stage of disease.
Potential Implementation Problems, Solutions and Alternative Strategies.
The proposed research activity will define a nanoscreening platform optimized to identify the PC able to discriminate between patients diagnosed with CC and NOP. Preliminary results reported above and the longstanding expertise on CC of University of Campus Bio-Medico of Rome give us a big confidence on the success of the project in its various phases. However, a problem may be the inability to generate shear stress capable of radically modifying the protein corona limiting in this way the optimization of the proposed technology. The limit lies in the use of a device working with delimited shear stress values. In this case, we think to solve the problem by printing, using a 3D printer, microfluidic channels with different sections and capacity that can allow us to vary the shear stress in an arbitrary manner. Furthermore, the proposed nanoparticles, even if accurately selected on the base of our experience, may not yield promising results. In this case the solution will be a screening of other nanoparticles. Our team has a broad experience with a huge variety of both inorganic and organic NPs. So alternative strategies, if needed, could be easily identified.