Engineering and Architecture
Universitat Rovira i Virgili/ICREA
Nanoscience, Materials and Chemical Engineering
Surface-enhanced Raman scattering (SERS) profiling of RNA from tumor educated platelets
The role of ribonucleic acids (RNAs) in cellular processes is one of the most dynamic and fast growing fields in biology, with new biological RNA-activities continuously emerging. Notably, mRNA contained in tumor-educated blood platelets (TEPs) has been shown to offer a new biosource to diagnose and classify common types of cancer using liquid biopsies (LBs). Blood-based LBs are attracting growing interest for early cancer diagnostics and treatment monitoring, as they potentially provide a non-invasive, low-cost alternative to standard surgical tissue biopsies. However, in the case of LBs based on RNA oncomarkers, RNA expression profiling is commonly obtained via sequencing which, while providing a high-throughput assay, presents major disadvantages; such as a high cost, a large amount of required RNA, and post-transcriptional modifications of the RNA molecules are not easily “readable” by this method. Therefore, the development of new strategies to detect RNA mutations in real samples represents a major breakthrough.
Nano-optical sensors, especially with plasmonic nanostructures, have drawn substantial interest in nanomedicine because of their ability to overcome key limitations of current techniques. In particular, surface-enhanced Raman scattering (SERS) spectroscopy has demonstrated tremendous potential for highly sensitive, multiplexed molecular detection with chemical structural molecular fingerprinting.
The ultimate objective of this project is to develop state-of-the-art nanotechnologies that will provide new cancer diagnostic tools, based on the ultra-sensitive, multiplexed SERS detection of mRNA onco-signatures with extremely high sensitivity (i.e.; PCR-free methods) in blood-based LBs. In particular, we will target mRNA mutations that are routinely screened in the diagnosis and prognosis of colorectal cancer (the 4th leading cause of cancer death in the world). To this end, we will couple specifically designed hybrid plasmonic materials with selective mRNA receptors, displaying a high binding affinity and specificity for the target mRNAs. The coupling between the plasmonic nanostructures and the RNA receptors will occur via a covalently linked spacer, acting as a SERS transducer. The mRNA target/receptor recognition events will translate into measurable alterations of the unique SERS spectra associated with the molecular reorientation/deformation of the transducer. Identification/characterization of the spectral markers that are more sensitive to such structural reorganization will be performed via DFT calculations.
This indirect SERS sensing strategy has already been successfully applied by our group using peptide-conjugate to detect oncoproteins in real blood samples (JACS 2016, 138, 14206; JACS 2013, 135, 10314). Implementation of the sensing strategy into a microfluidic device will further help to reduce the required amount of nucleic acids per measurement while enabling on-line monitoring of large volumes of the sample.
37.5 hours a week
|This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 713679|