New therapy for pancreatic cancer based on extracellular vesicles

• Published in: Biomedicine & pharmacotherapy 2023-06, Vol.162, p.114657-114657, Article 114657
• Main Authors: Araujo-Abad, Salomé, Manresa-Manresa, Antonio, Rodríguez-Cañas, Enrique, Fuentes- Baile, María, García-Morales, Pilar, Mallavia, Ricardo, Saceda, Miguel, de Juan Romero, Camino
• Format: Article
• Language: English
• Subjects: Carcinoma, Pancreatic Ductal - pathology; Cell Line, Tumor; Chemotherapy; Extracellular Vesicles - metabolism; FESEM; Humans; Nanocarriers; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; Protein-Arginine N-Methyltransferases - metabolism; Small EVs
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114657

Pancreatic Ductal Adenocarcinoma (PDAC), is the most common aggressive cancer of the pancreas. The standard care of PDAC includes tumor resection and chemotherapy, but the lack of early diagnosis and the limited response to the treatment worsens the patient’s condition. In order to improve the efficiency of chemotherapy, we look for more efficient systems of drug delivery. We isolated and fully characterized small Extracellular Vesicles (EVs) from the RWP-1 cell line. Our study indicates that the direct incubation method was the most efficient loading protocol and that a minimum total amount of drug triggers an effect on tumor cells. Therefore, we loaded the small EVs with two chemotherapeutic drugs (Temozolomide and EPZ015666) by direct incubation method and the amount of drug loaded was measured by high-performance liquid chromatography (HPLC). Finally, we tested their antiproliferative effect on different cancer cell lines. Moreover, the system is highly dependent on the drug structure and therefore RWP-1 small EVsTMZ were more efficient than RWP-1 small EVsEPZ015666. RWP-1 derived small EVs represent a promising drug delivery tool that can be further investigated in preclinical studies and its combination with PRMT5 inhibitor can be potentially developed in clinical trials for the treatment of PDAC. [Display omitted] •Small EVs derived from RWP-1 are good drug carriers for PDAC treatment.•RWP-1 small EVs provide more efficiency than direct administration of the drugs at very low doses.•Efficiency of a therapy based on RWP-1 derived small EVs is highly dependent on the chemical structure of the drug.