Abstract
HiSENSE4MED aims to develop high-resolution, smart engineered sensing platforms to dynamically monitor metabolic and interaction heterogeneity in advanced disease models, driving innovation toward next-generation precision medicine. The project creates multifunctional micro-nanosystems embedding optical sensors for key analytes (e.g., pH, oxygen, potassium, lactate) within nano/microparticles, electrospun nanofibers, hydrogels, and 3D-printed scaffolds. These platforms will noninvasively track chemical gradients in intracellular organelles, co-cultures, spheroids, organoids, organ-on-chips, and ex vivo tissues, extending also to in vivo models. Integrating high resolution live-cell fluorescence microscopy, computational modelling, and mechanistic reconstruction, HiSENSE4MED will reveal how cancer, immune and stromal cells interact to remodel their microenvironment, and drive drug resistance. Building on ERC-StG INTERCELLMED, AIRC-MFAG-2019, PNC-Fit4MedRob and ERC-POC HySENSE achievements, and aligned with the Centro per la Medicina di Precisione TecnoMed di Lecce, HiSENSE4MED will deliver innovative tools for rapid in vitro, ex vivo and in vivo drug screening and personalized therapy forecasting, advancing sensor commercialization and opening new paths in cancer diagnostics and precision medicine.
Objectives
- Objective 1 - Multifunctional Sensors for Metabolic Profiling in Cancer Apply advanced ratiometric optical sensors based on nano- and microparticles, electrospun fibers, hydrogels, and 3D-printed scaffolds to map dynamic concentration changes of H⁺, O₂, K⁺, and lactate in 2D/3D patient-derived models of pancreatic cancer, melanoma, rheumatoid arthritis, colon cancer, Parkinson’s disease, glioblastoma and B-cell non-Hodgkin lymphoma.
- Objective 2 –- Intracellular Dynamic pH Monitoring in Neurodegeneration Employ optical ratiometric pH sensors to monitor real-time intracellular acidification in wild- type and knockout cells of human neurodegenerative models (e.g., Parkinson’s) exhibiting altered endosomal/lysosomal activity, using time-lapse confocal microscopy, deep learning- based particle segmentation and object tracking algorithms, and dynamic pH analysis to quantify differences in organelle acidification kinetics and mechanistic pathways.
- Objective 3 – High-Resolution Imaging of Single-Cell Metabolic Dynamics Develop advanced four-dimensional fluorescence imaging and correlative microscopy approaches, combining high-resolution live-cell fluorescence microscopy with X-ray, and electron and ion microscopy, to analyze single-cell metabolic fluxes, ionic gradients, and microenvironmental remodeling in ex vivo tissues and in vivo models, enabling predictive drug screening and therapy response profiling.
Collaborators
- University of North Carolina at Chapel Hill (USA)
- Federal University of Paraná (UFPR) (Br)
- Ludwig Maximilian University of Munich (DE)
- Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine (NL)
- 3B’s Research Group, Institute of Biomaterials, Biodegradables and Biomimetics (3Bs), University of Minho (PG)
- Biofisika Institute (ES)
- University of Santiago de Compostela (ES)
- University of Salento, Lecce (IT)
- Italian Institute of Technology (IIT) (IT)
- Institute of Genetics and Biophysics (IGB), CNR (IT)
- Institute of Biochemistry and Cell Biology (IBBC), CNR (IT)
- Institute of Electronics, Computer and Telecommunication Engineering (IEIIT), CNR (IT)
- Telethon Institute of Genetics and Medicine (TIGEM) (IT)
- University of Genoa (IT)
- University of Naples "Federico II" and Italian Institute of Technology (IIT) (IT)
- Polytechnic University of Turin (Politecnico di Torino) (IT)
- CNR-Nanotec Institute, National Research Council (CNR) (IT)
- University of Bologna (IT)
- IRCCS University Hospital of Bologna (IT)
- Vito Fazzi Hospital, Lecce (IT)
Key 5 publications
- 1. Engineered Ratiometric Sensory Electrospun Fibers for Oxygen Mapping in Complex Cultures and Tumor Microenvironment. G. Grasso, S. Forciniti, V. Onesto, L. Pierantoni, D. Caballero, E. D’Amone, G. Gigli, Rui L. Reis, J.M. Oliveira, L.L. del Mercato, Biosensors and Bioelectronics, 2025.
- 2. A 3D Pancreatic Cancer Model with Integrated Optical Sensors for Noninvasive Metabolism Monitoring and Drug Screening, A.C. Siciliano, S. Forciniti, V. Onesto, H. Iuele, D. Delle Cave, F. Carnevali, G. Gigli, E. Lonardo. L.L. del Mercato, Advanced Healthcare Materials 13 (29), 2470188, 2024.
- 3. Quantifying heterogeneity to drug response in cancer–stroma kinetics. F. Alemanno, M. Cavo, D. Delle Cave, A. Fachechi, R. Rizzo, E D’Amone, G. Gigli, E. Lonardo, A. Barra, L.L del Mercato, PNAS 120 (11), e2122352120, 2023.
- 4. Probing single cell fermentation fluxes and exchange networks via pH-sensing hybrid nanofibers. V Onesto, S Forciniti, F Alemanno, K Narayanankutty, A Chandra, S. Prasad, A. Azzariti, G. Gigli, A. Barra, A. De Martino, D. De Martino, L.L. del Mercato, ACS Nano 17 (4), 3313, 2023.
- 5. Fully automated computational approach for precisely measuring organelle acidification with optical pH sensors. A. Chandra, S. Prasad, F. Alemanno, M. De Luca, R. Rizzo, R. Romano, G. Gigli, C. Bucci, A. Barra, L.L. del Mercato, ACS applied materials & interfaces 14 (16), 18133, 2022.
People
- Roberta Bove
- Federica Carnevali
- Manuela Cedrùn Morales
- Francesco Colella
- Stefania Forciniti
- Giuliana Grasso
- Helena Iuele
- Valentina Onesto
- Enrica Soprano
- Anna Chiara Siciliano
- Giulia Vanoni
