Biology subjects

Tassoni, S.

Publications and source records attributed to Tassoni, S..

2 recordsLinked to original sources

bioRxiv2025

Red blood Cell-derived Extracellular Vesicles as biomaterials: the opportunity of freezing-induced accelerated aging

Red blood cell-derived extracellular vesicles (RBC-EVs) are emerging as promising biomaterials for next-generation drug delivery, due to their inherent biocompatibility, immune evasion capabilities, and minimal oncogenic risk. However, their clinical translation remains limited by unresolved challenges related to heterogeneity, reproducibility, and long-term storage. This study proposes a method that leverages freezing-induced ageing for obtaining highly homogeneous RBC-EV batches, an important step towards using RBC-EVs as healthcare biomaterials and advancing their clinical translation in EV-based nanomedicine. This method was made possible thanks to the analytical support of discontinuous sucrose density gradient and high-resolution interferometric nanoparticle tracking analysis, which allowed the identification of a bimodal subpopulation distribution, in terms of vesicle size, interferometric contrast, and subpopulation profiles, in freshly prepared samples, and then tracked how long-term cold storage at -80 {degrees}C channeled this heterogeneity into a monomodal population. Finally, we evaluated the functionality of homogenized RBC-EV samples by assessing surface-associated enzymatic activity and uptake in cancer cell lines, demonstrating that freeze-thaw-induced accelerated-aging provides a viable strategy for producing RBC-EV preparations that retain membrane integrity and remain readily internalized by cells. These findings offer valuable insights into the optimization and standardization of RBC-EV handling and storage protocols, providing a foundation for their reliable integration into EV-based therapeutic applications.

cell biology↗

bioRxiv2025

Red Blood Cell-derived Extracellular Vesicles enable Cisplatin and Cetuximab Synergistic Therapy against Triple-Negative Breast Cancer

BackgroundTriple-negative breast cancer is an aggressive breast cancer subtype characterized by the absence of human epidermal growth factor receptor 2, estrogen and progesterone receptors, limiting targeted therapy options. Cisplatin, a chemotherapeutic agent, induces DNA damage and exhibits some efficacy against triple-negative breast cancer, but its effectiveness is often reduced by chemoresistance and systemic toxicity. A very promising strategy to augment cisplatin treatment can be based on combining it with the biologic Cetuximab, an epidermal growth factor receptor inhibitor, which boosts cisplatin efficacy by inducing ferroptosis. ResultsTo optimize this strategy in a biocompatible and precise manner, we developed a nanoplatform based on red blood cell-derived extracellular vesicles for the combined delivery of Cetuximab and cisplatin, enabling immune evasion, and the possibility of autologous personalization and GMP-compliant production. Owing to their DNA-free lumen and lack of EGFR, RBC-EVs preserve cisplatin activity and prevent interference with cetuximab. This formulation enhances cisplatins cytotoxicity by up to 50%, as shown in vitro and in patient-derived organoids. It effectively reduces chemoresistance by downregulating hypoxia-related genes and promoting ferroptosis, additionally, it improves cisplatins cytotoxic effects while reducing hemotoxicity compared to the administration of free cisplatin. ConclusionsThese findings highlight the potential of red blood cell-derived extracellular vesicles as a biocompatible delivery system enabling combined therapy and offering a promising strategy to overcome current limitations in TNBC treatment.

cell biology↗