Journal of nanobiotechnology · 2026
Red blood cell-derived extracellular vesicles enable cisplatin and cetuximab combined therapy against triple-negative breast cancer.
СтатьяНазвание и аннотация: Перевод в очереди
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Romano Miriam, Musicò Angelo, Tassoni Selene, Paolini Lucia, Zendrini Andrea, Gilberti Enrica, Orlandi Francesca, Pedrazzi Tatiana, Alacqua Silvia, Segala Agnese, Zenatelli Rossella, Cifola Ingrid, Mangano Eleonora, Consolandi Clarissa, Camboni Tania, Signati Lorena, Mazzucchelli Serena, Neva Arabella, Ragni Maurizio, Severgnini Marco, Valerio Alessandra, Pomarico Giuseppe, Almici Camillo, De Palma Giuseppe, Corsi Fabio, Bergese Paolo, Radeghieri Annalisa
Аннотация
BACKGROUND: Triple-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.
RESULTS: To 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 cisplatin's 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 cisplatin's cytotoxic effects while reducing hemotoxicity compared to the administration of free cisplatin.
CONCLUSIONS: These 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.
RESULTS: To 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 cisplatin's 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 cisplatin's cytotoxic effects while reducing hemotoxicity compared to the administration of free cisplatin.
CONCLUSIONS: These 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.