New therapy for pancreatic cancer based on extracellular vesicles

by Selleckchem | Jun 25 2023

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.

Comments:

Your study focused on exploring the potential of small extracellular vesicles (EVs) derived from the RWP-1 cell line as a drug delivery system for pancreatic ductal adenocarcinoma (PDAC). PDAC is a highly aggressive cancer of the pancreas, and current treatment options, including tumor resection and chemotherapy, have limited effectiveness due to challenges in early diagnosis and the tumor's resistance to therapy.

To enhance the efficiency of chemotherapy, you investigated different methods of loading chemotherapeutic drugs into small EVs isolated from the RWP-1 cell line. The direct incubation method was found to be the most effective loading protocol. Additionally, your study revealed that a minimum total amount of drug was sufficient to induce a therapeutic effect on tumor cells.

You loaded the small EVs with two chemotherapeutic drugs, Temozolomide (TMZ) and EPZ015666, and quantified the amount of drug loaded using high-performance liquid chromatography (HPLC). Subsequently, you evaluated the antiproliferative effects of the drug-loaded small EVs on various cancer cell lines. The results indicated that the efficiency of drug delivery varied depending on the drug structure, with RWP-1 small EVs loaded with TMZ demonstrating higher efficacy compared to RWP-1 small EVs loaded with EPZ015666.

Based on these findings, you conclude that RWP-1-derived small EVs hold promise as a drug delivery tool for PDAC. Further investigation through preclinical studies is warranted to explore their potential in more detail. Additionally, you suggest that combining RWP-1 small EVs with a PRMT5 inhibitor may offer a potential therapeutic strategy that could be further developed and evaluated in clinical trials for the treatment of PDAC.

Overall, your study highlights the potential of utilizing small EVs derived from the RWP-1 cell line as an efficient drug delivery system for PDAC, providing insights into improving the efficacy of chemotherapy and potential avenues for future research and clinical applications.