Written by Federico Citterich
Conceived and reviewed by Alessandro Rossetta
Despite previous failures in early pancreatic cancer detection, researchers have found hope in a disease-specific “protein corona” that forms around nanoparticles. The EU-funded LaserBlood project is now exploring this unique biological fingerprint using light-based technology, with the goal of developing a fast, reliable blood test for early diagnosis.
“But there is a glimmer of light at the end of the tunnel…”, that’s how we signed off our previous issue, Pancreatic Cancer: Why Are Early Detection Methods Still Absent in 2025?, after exploring the challenges and failures in developing reliable screening tools for this devastating disease. And when we spoke of a “glimmer of light,” we weren’t being purely metaphorical — we meant it quite literally. Let’s follow that light a little further.
As outlined in our previous issue, biomarker detection has emerged as a promising approach for diagnosing pancreatic cancer at an early stage. This technique involves identifying cancer-associated molecules or biological signatures in patients, enabling earlier intervention. However, a significant challenge has persisted: most biomarkers identified to date lack sufficient specificity. While many are indeed present in cases of pancreatic cancer, they are also found in a range of other medical conditions, increasing the risk of false positives.
A notable breakthrough occurred when researchers began to investigate the interactions between nanomaterials1 – such as nanoparticles2 – and the body fluids of cancer patients, such as plasma3, saliva, gastric fluid, etc. When nanoparticles come into contact with biological fluids they are rapidly coated by a dense layer of biomolecules that adsorb onto their surface. This layer, composed of proteins, lipids, sugars, and other molecules, is predominantly made up of proteins, and is therefore commonly referred to as the “protein corona”. Importantly, the composition of the protein corona is disease-specific, making it a potential tool for identifying particular types of cancer.
Schematic of the formation of the protein corona. 1) A patient affected by pancreatic cancer; 2) A nanoparticle comes into contact with the patient’s blood: 3) Proteins rapidly coat around the nanoparticle; 4) A disease-specific protein corona is formed.
However, the potential for using protein corona characterization in clinical screening is hindered by two key challenges. First, the absence of early diagnostic methods for pancreatic cancer in the general population makes it extremely difficult, if not impossible, to identify the protein corona in the early stages of the disease. Second, isolating proteins for nanopartciles and directly measuring the composition of the protein corona is challenging due to the complex and time-consuming methods required, which involve multiple steps and can result in significant variability in the experimental results. So, is there a way around these limitations? Can we actually harness the protein corona for early cancer detection, despite the hurdles?
That’s exactly what the LaserBlood project is setting out to explore. Funded by the European Union as part of the EIC Pathfinder program, LaserBlood is on a mission to develop a breakthrough technology for spotting pancreatic cancer early – by zeroing in on the unique fingerprint left by the protein corona.
To overcome the challenge of detecting pancreatic cancer early, LaserBlood is working with experts from the Istituto Nazionale Tumori Regina Elena (IFO-IRE), who have developed a special type of lab mouse that mimics how pancreatic cancer grows in humans. These mice carry a genetic mutation that causes them to develop pancreatic tumors in a predictable way. Even before the tumors become noticeable, early warning signs – called precancerous lesions – start to appear. This gives researchers a rare and valuable window to study the disease in its earliest stages. By analyzing the protein corona during these early phases, the team hopes to identify clear markers that could one day be used to spot pancreatic cancer in people long before symptoms appear.
What about the problem of analyzing the protein corona itself? As explained by a paper by Caputo et al., traditional methods for studying it are slow, complicated, and often produce inconsistent results. To make things faster and more reliable, LaserBlood is taking a different approach. Instead of isolating and analyzing proteins one by one, the project uses light – quite literally picking up the glimmer we mentioned at the very start – and in particular a special kind of light-based technology. When nanoparticles coated with the protein corona are hit with a laser, they give off a unique glow – like a fingerprint – that can reveal whether pancreatic cancer is present.
LaserBlood is still in its early stages, but its approach holds real promise for changing the landscape of pancreatic cancer detection. By combining cutting-edge nanotechnology, advanced biophotonics techniques, and deep biological insight, the project aims to deliver a fast, accurate, and minimally invasive blood-based test that could one day become a routine part of clinical screenings. If successful, this glimmer of light could grow into a powerful beacon – one that helps detect pancreatic cancer earlier, treat it more effectively, and ultimately save lives.
GLOSSARY
- Nanomaterials are materials with structural features at the nanoscale (typically 1–100 nanometers), which often give them unique physical, chemical, or biological properties.
- Nanoparticles are types of nanomaterials that exist as discrete particles with all three dimensions in the nanoscale range.
- Plasma is the liquid component of blood, making up about 55% of its total volume. It is primarily composed of water, along with proteins, electrolytes, hormones, nutrients, and waste products, and serves as the medium for transporting blood cells and various substances throughout the body.
REFERENCES
Caputo, D., Digiacomo, L., Cascone, C., Pozzi, D., Palchetti, S., Di Santo, R., … & Caracciolo, G. (2020). Synergistic analysis of protein corona and haemoglobin levels detects pancreatic cancer. Cancers, 13(1), 93.
https://www.mdpi.com/2072-6694/13/1/93
Caputo, D., Quagliarini, E., Pozzi, D., & Caracciolo, G. (2022). Nanotechnology meets oncology: a perspective on the role of the personalized nanoparticle-protein corona in the development of technologies for pancreatic cancer detection. International Journal of Molecular Sciences, 23(18), 10591.
https://www.mdpi.com/1422-0067/23/18/10591
Digiacomo, L., Jafari-Khouzani, K., Palchetti, S., Pozzi, D., Capriotti, A. L., Laganà, A., … & Caracciolo, G. (2020). A protein corona sensor array detects breast and prostate cancers. Nanoscale, 12(32), 16697-16704.
https://pubs.rsc.org/en/content/articlelanding/2020/nr/d0nr03439h/unauth
Docter, D., Strieth, S., Westmeier, D., Hayden, O., Gao, M., Knauer, S. K., & Stauber, R. H. (2015). No king without a crown–impact of the nanomaterial-protein corona on nanobiomedicine. Nanomedicine, 10(3), 503-519.
https://www.tandfonline.com/doi/abs/10.2217/nnm.14.184
Hajipour, M. J., Laurent, S., Aghaie, A., Rezaee, F., & Mahmoudi, M. (2014). Personalized protein coronas: a “key” factor at the nanobiointerface. Biomaterials science, 2(9), 1210-1221.
https://pubs.rsc.org/en/content/articlehtml/2014/bm/c4bm00131a
Ke, P. C., Lin, S., Parak, W. J., Davis, T. P., & Caruso, F. (2017). A decade of the protein corona. ACS nano, 11(12), 11773-11776.
https://pubs.acs.org/doi/abs/10.1021/acsnano.7b08008
Monopoli, M. P., Walczyk, D., Campbell, A., Elia, G., Lynch, I., Baldelli Bombelli, F., & Dawson, K. A. (2011). Physical− chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. Journal of the American Chemical Society, 133(8), 2525-2534.
https://pubs.acs.org/doi/abs/10.1021/ja107583h