I grew up as a scientist at the bio-nano frontier, where I realized colloid and surface chemistry can raise and answer original biological questions. Today, totally fascinated by biogenic nanoparticles, I head a multidisciplinary team featuring one of the first stories of integration of chemistry, nanotechnology and molecular biology in extracellular nanoparticle research.
RESEARCH, TEACHING, or OTHER INTERESTS
General Chemistry, Physical and Theoretical Chemistry, Biotechnology, Biophysics
Unraveling the Heterogeneity of Cargo Distribution in the Exogenous Association of Proteins With Extracellular Vesicles Karl Normak, Marcell Papp, Carolina Paganini, Andrea Zendrini, Paolo Bergese, et al. Advanced Healthcare Materials, 2026 Extracellular vesicles (EVs) are emerging as promising nanocarriers for delivering molecules, including proteins. Various exogenous methods are proposed for loading EVs with specific cargo proteins. While the loading yield and the heterogeneity of cargo distribution are crucial quality attributes, a comprehensive quantification of these properties is still lacking. Here, we characterize the heterogeneity of EVs loaded with a model cargo protein, GFP, using various exogenous methods. A combination of biophysical methods is applied to quantify the overall yield and cargo distribution at both the ensemble and single‐particle levels. Among the loading methods evaluated, electroporation is most effective for associating GFP with EVs. However, the GFP molecules per vesicle is fewer than 100, representing approximately 4% of the maximum protein capacity that EVs can potentially accommodate. Across all loading methods, the distribution of protein content per vesicle displays significant heterogeneity and follows an exponential decay function, with a higher prevalence of vesicles featuring lower protein content and fewer with higher content. Moreover, loading efficiency increases with EV size. This study shows that overall yields of exogenous loading methods to associate proteins with EVs remain modest and the resulting distribution of cargo proteins associated with EVs is highly heterogeneous.
The gold nanoparticle-lipid membrane synergy for nanomedical applications Lucrezia Caselli, Lucia Paolini, Wye-Khay Fong, Costanza Montis, Andrea Zendrini, et al. Nanoscale Horizons, 2025 The integration of gold nanoparticles (AuNPs) with lipid bilayers, gives rise to powerful synergistic effects arising from nanoscale interactions.
Nanoplasmonic Isosbestics Uncover Mesoscale Assembly of Gold Nanoparticles on Soft Templates Jacopo Cardellini, Ilaria De Santis, Giuseppe Emanuele Lio, Marco Brucale, Francesco Valle, et al. Journal of the American Chemical Society, 2025 Assembly of plasmonic nanoparticles (NPs) generates unique optical properties through coupling of the localized surface plasmon resonance (LSPR) of individual NPs. However, precisely controlling and monitoring how mesoscale assembly dictates final optical properties remain key challenges in designing advanced plasmonic materials. Here, we introduce "nanoplasmonic isosbestics" as optical descriptors of the mesoscale organization of gold nanoparticles (AuNPs) on soft templates. Unlike isosbestic points in molecular spectroscopy, which describe chemical equilibria, our numerical simulations demonstrate that nanoplasmonic isosbestics emerge from the coexistence of individual AuNPs and AuNP clusters, where the interparticle spacing determines the isosbestic wavelength. By templating AuNP assembly onto synthetic free-standing lipid bilayers with tunable membrane rigidity, we experimentally achieve precise control over interparticle spacing and prove that it is mirrored by univocal modulation of the isosbestic wavelength. This provides a fundamental understanding of the structure-function relationship in plasmonic systems, linking, for the first time, nanoplasmonic isosbestics to interparticle spacing and equilibrium structure in plasmonic assemblies. On the analytical perspective, nanoplasmonic isosbestics provide noninvasive optical fingerprints of the templates, opening to appealing applications. As a proof of concept, we apply this approach to profile the stiffness of two extracellular vesicle (EVs) classes─mesenchymal stem cell (MSC)-derived and red blood cell-derived EVs─both recognized for their biological and translational potential.
MicroRNA-142-3p shuttling in extracellular vesicles marks regulatory T cell dysfunction in multiple sclerosis Giusy De Rosa, Claudia Russo, Silvia Garavelli, Dario Di Silvestre, Ilaria Spatocco, et al. Science Translational Medicine, 2025 CD4 + CD25 hi FoxP3 + regulatory T cells (T reg cells) are key controllers of immune self-tolerance, and their suppressive function is impaired in people with relapsing-remitting multiple sclerosis (pwRR-MS). Because the mechanisms underlying this condition are still ill-defined, we investigated the role of T reg cell–derived extracellular vesicles (T reg -EVs) in T reg cell dysfunction observed in pwRR-MS. We found that T reg -EVs from healthy individuals inhibit CD4 + conventional T (T conv ) cells by shuttling miR-142-3p from the T reg cell to the T conv cell. There, miR-142-3p down-regulated mRNAs necessary for T conv cell growth and effector functions, such as the redox controller cystine carrier SLC7A11 . However, T reg cells from pwRR-MS released EVs containing reduced amounts of miR-142-3p, resulting in impaired suppressive function. Furthermore, T reg -EV miR-142-3p inversely correlated with the disability score and gadolinium-enhancing lesions in pwRR-MS. Together, our results elucidate a molecular mechanism involving miR-142-3p shuttled by T reg -EVs in the control of immune self-tolerance and unveil its pathogenetic implications in human autoimmunity.
Extracellular vesicles in regenerative medicine Miriam Romano, Andrea Zendrini, Lucia Paolini, Sara Busatto, Anna C. Berardi, et al. Nanomaterials for Theranostics and Tissue Engineering Techniques Trends and Applications, 2020
The nanostructured secretome S. Busatto, A. Zendrini, A. Radeghieri, L. Paolini, M. Romano, et al. Biomaterials Science, 2020
Unraveling the Heterogeneity of Cargo Distribution in the Exogenous Association of Proteins With Extracellular Vesicles K Normak, M Papp, C Paganini, A Zendrini, P Bergese, D Pinotsi, ... Advanced Healthcare Materials 15 (10), e2403991 , 2026 2026 Citations: 2
A reliable high-throughput OECT-based bioelectronic system enabling pan-specific vesicle quantification G Frusconi, A Musicò, A Zendrini, ZM Kovács-Vajna, L Paolini, P Bergese, ... Biosensors and Bioelectronics: X, 100755 , 2026 2026 Citations: 1
Ethanol-Guided Hybridization of Extracellular Vesicles with Liquid-Crystalline Lipid Nanoparticles V Pacciani, J Cardellini, A Balestri, M Rojas-Rodríguez, M Calamai, ... ACS Applied Materials & Interfaces , 2026 2026 Citations: 2
Investigating the effect of ginger-derived nanovesicles on the growth and metabolic activity of Bacteroides thetaiotaomicron : an isothermal microcalorimetric study F Loria, A Kattel, M Brucale, F Valle, P Bergese, EG Kobrin, A Chiesi, ... bioRxiv, 2026.01. 08.698378 , 2026 2026
Orthogonal investigation at single-particle and ensemble levels uncovers lipoprotein-extracellular vesicle binding A Musicò, R Frigerio, K Normak, S Scolari, A Gori, P Arosio, A Radeghieri, ... Analytical Chemistry , 2026 2026
Red blood cell-derived extracellular vesicles as biomaterials: the opportunity of freezing-induced accelerated aging L Paolini, M Romano, V Mangolini, S Tassoni, S Jiang, EL Mazzoldi, ... Biomaterials Science 14 (1), 122-139 , 2026 2026 Citations: 3
Spotlight on innovation: key insights from the extracellular vesicle cluster meeting at the European Innovation Council G Adamo, I Amarantos, I Arzimanoglou, P Bergese, B Bussolati, ... Cytotherapy , 2025 2025 Citations: 2
The extracellular vesicle biomolecular corona: current insights and diagnostic potential S Tassoni, P Bergese, A Radeghieri Nanomedicine 20 (16), 2013-2021 , 2025 2025 Citations: 11
A flexible separation method improves the comprehension of extracellular vesicles and exomeres’ function. Focus on metalloproteinase-9 secreted by different tumor cell lines F Accattatis, L Bianchi, Z Tang, F Imbò, M Brucale, F Valle, P Bergese, ... Atherosclerosis 407 , 2025 2025
Extracellular vesicle isolation and characterization from bottlenose dolphin’s (Tursiops truncatus) breath V Moccia, C Centelleghe, A Zendrini, G Pesce, E Alvarez, E Esposti, ... Journal of Comparative Pathology 220, 58 , 2025 2025
Hybrid Biogenic Lipid Nanoparticles: leveraging hybridization with Extracellular Vesicles for enhancing biocompatibility and targeting efficiency L Caselli, V Pacciani, J Cardellini, A Balestri, A Zendrini, L Paolini, ... EUROPEAN BIOPHYSICS JOURNAL 54, S55-S55 , 2025 2025
Preparation and Multiscale Analytical Characterization of Nanoparticle-extracellular Vesicle Hybrids J Cardellini, K Normak, M Gerlt, A Bongiovanni, P Bergese, P Arosio EUROPEAN BIOPHYSICS JOURNAL 54, S147-S147 , 2025 2025
Nanoplasmonic Isosbestics uncover mesoscale assembly of gold nanoparticles on soft templates J Cardellini, I De Santis, GE Lio, M Brucale, F Valle, V Catani, I Mastrolia, ... Journal of the American Chemical Society 147 (23), 20008-20022 , 2025 2025 Citations: 7
MicroRNA-142-3p shuttling in extracellular vesicles marks regulatory T cell dysfunction in multiple sclerosis G De Rosa, C Russo, S Garavelli, D Di Silvestre, I Spatocco, G Mele, ... Science Translational Medicine 17 (800), eadl1698 , 2025 2025 Citations: 6
Red Blood Cell-derived Extracellular Vesicles enable Cisplatin and Cetuximab combined Therapy against Triple-Negative Breast Cancer M Romano, A Musicò, A Zendrini, E Gilberti, F Orlandi, T Pedrazzi, ... bioRxiv, 2025.03. 20.644320 , 2025 2025
Microfluidics‐Driven Manufacturing and Multiscale Analytical Characterization of Nanoparticle‐Vesicle Hybrids J Cardellini, K Normak, M Gerlt, K Makasewicz, C Seiffert, ... Advanced healthcare materials 14 (4), 2403264 , 2025 2025 Citations: 13
Unveiling the mesoscale assembly of gold nanoparticles on soft templates via nanoplasmonic isosbestic points I De Santis, J Cardellini, GE Lio, M Brucale, F Valle, V Catani, I Mastrolia, ... Book of Abstract-CDCF50&5thECPC Conference, 0-0 , 2025 2025
The gold nanoparticle–lipid membrane synergy for nanomedical applications L Caselli, L Paolini, WK Fong, C Montis, A Zendrini, J Cardellini, ... Nanoscale Horizons 10 (9), 1863-1881 , 2025 2025 Citations: 13
Red Blood Cell-derived Extracellular Vesicles enable Cisplatin and Cetuximab Synergistic Therapy against Triple-Negative Breast Cancer M Romano, A Musicò, A Zendrini, E Gilberti, F Orlandi, T Pedrazzi, ... bioRxiv , 2025 2025
Helminth extracellular vesicles co‐opt host monocytes to drive T cell anergy A Borup, MF Sharifpour, LS Rossen, B Whitehead, AT Boysen, R Olesen, ... Journal of Extracellular Vesicles 14 (1), e70027 , 2025 2025 Citations: 7
MOST CITED SCHOLAR PUBLICATIONS
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the … C Théry, KW Witwer, E Aikawa, MJ Alcaraz, JD Anderson, ... Journal of extracellular vesicles 7 (1), 1535750 , 2018 2018 Citations: 12089
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches JA Welsh, DCI Goberdhan, L O'Driscoll, EI Buzas, C Blenkiron, ... Journal of extracellular vesicles 13 (2), e12404 , 2024 2024 Citations: 4071
Tangential flow filtration for highly efficient concentration of extracellular vesicles from large volumes of fluid S Busatto, G Vilanilam, T Ticer, WL Lin, DW Dickson, S Shapiro, ... Cells 7 (12), 273 , 2018 2018 Citations: 591
Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop AE Russell, A Sneider, KW Witwer, P Bergese, SN Bhattacharyya, ... Journal of extracellular vesicles 8 (1), 1684862 , 2019 2019 Citations: 298
On the issue of transparency and reproducibility in nanomedicine HS Leong, KS Butler, CJ Brinker, M Azzawi, S Conlan, C Dufès, A Owen, ... Nature nanotechnology 14 (7), 629-635 , 2019 2019 Citations: 249
Nolte-’t Hoen EN C Théry, KW Witwer, E Aikawa, MJ Alcaraz, JD Anderson, ... Noren Hooten N , 2018 2018 Citations: 227
Residual matrix from different separation techniques impacts exosome biological activity L Paolini, A Zendrini, GD Noto, S Busatto, E Lottini, A Radeghieri, A Dossi, ... Scientific reports 6 (1), 23550 , 2016 2016 Citations: 208
AFM-based high-throughput nanomechanical screening of single extracellular vesicles A Ridolfi, M Brucale, C Montis, L Caselli, L Paolini, A Borup, AT Boysen, ... Analytical chemistry 92 (15), 10274-10282 , 2020 2020 Citations: 162
Exosome-delivered microRNAs promote IFN-α secretion by human plasmacytoid DCs via TLR7 V Salvi, V Gianello, S Busatto, P Bergese, L Andreoli, U D’Oro, A Zingoni, ... JCI insight 3 (10), e98204 , 2018 2018 Citations: 135
Colorimetric nanoplasmonic assay to determine purity and titrate extracellular vesicles D Maiolo, L Paolini, G Di Noto, A Zendrini, D Berti, P Bergese, D Ricotta Analytical chemistry 87 (8), 4168-4176 , 2015 2015 Citations: 122
Embodied energy as key parameter for sustainable materials selection: The case of reusing coal fly ash for removing anionic surfactants A Zanoletti, S Federici, L Borgese, P Bergese, M Ferroni, LE Depero, ... Journal of Cleaner Production 141, 230-236 , 2017 2017 Citations: 98
Merging colloidal nanoplasmonics and surface plasmon resonance spectroscopy for enhanced profiling of multiple myeloma-derived exosomes G Di Noto, A Bugatti, A Zendrini, EL Mazzoldi, A Montanelli, L Caimi, ... Biosensors and Bioelectronics 77, 518-524 , 2016 2016 Citations: 98
Interaction of nanoparticles with lipid membranes: a multiscale perspective C Montis, D Maiolo, I Alessandri, P Bergese, D Berti Nanoscale 6 (12), 6452-6457 , 2014 2014 Citations: 98
Large‐scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop L Paolini, M Monguió‐Tortajada, M Costa, F Antenucci, M Barilani, ... Journal of Extracellular Biology 1 (10), e63 , 2022 2022 Citations: 86
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J Extracell Vesicles. 2024; 13 (2): e12404 JA Welsh, DCI Goberdhan, L O’Driscoll, EI Buzas, C Blenkiron, ... Epub 2024/02/08. https://doi. org/10.1002/jev2. 12404 PMID: 38326288 13 (5 … , 2024 2024 Citations: 85
Fourier-transform Infrared (FT-IR) spectroscopy fingerprints subpopulations of extracellular vesicles of different sizes and cellular origin L Paolini, S Federici, G Consoli, D Arceri, A Radeghieri, I Alessandri, ... Journal of extracellular vesicles 9 (1), 1741174 , 2020 2020 Citations: 84
Microwave generated nanocomposites for making insoluble drugs soluble P Bergese, I Colombo, D Gervasoni, LE Depero Materials Science and Engineering: C 23 (6-8), 791-795 , 2003 2003 Citations: 84
The physico-chemical landscape of extracellular vesicles M Manno, A Bongiovanni, L Margolis, P Bergese, P Arosio Nature Reviews Bioengineering 3 (1), 68-82 , 2025 2025 Citations: 81
Surfactant titration of nanoparticle–protein corona D Maiolo, P Bergese, E Mahon, KA Dawson, MP Monopoli Analytical chemistry 86 (24), 12055-12063 , 2014 2014 Citations: 72
Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study C Gissi, A Radeghieri, C Antonetti Lamorgese Passeri, M Gallorini, ... PloS one 15 (3), e0229914 , 2020 2020 Citations: 71