Source abstract
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a highly fatal malignancy, with inadequate therapeutic strategies and an adverse prognosis. Gene therapy raises a prospective option to overcome the challenges posed by conventional therapeutic strategies. The CX3CL1-CX3CR1 axis plays a critical role in promoting tumor cell proliferation, migration, and metastasis in PDAC. Targeted delivery of small interfering RNA (siRNA) against CX3CR1 through M1 phenotype macrophage extracellular vesicles is a potential strategy to achieve accurate PDAC treatment. This study sought to investigate the therapeutic potential of siRNA specifically targeting CX3CR1 in PDAC via loading into extracellular vesicles (EVs) derived from M1 macrophages, evaluating its therapeutic efficacy through in vitro and in vivo experiments. The results demonstrated that siCX3CR1 was successfully incorporated into extracellular vesicles originating from M1 macrophages. M1 EV/siCX3CR1 significantly inhibited the proliferation and migration of AsPC-1 cells in vitro. In the AsPC-1 subcutaneously transplanted tumor model, M1 EV/siCX3CR1 also exhibited a significant tumor-suppressive effect. Overall, the loading of siCX3CR1 into M1 EVs holds promise as a potential therapeutic approach for pancreatic cancer treatment in the future.
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Affiliations
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology
Sichuan University
Department of Head and Neck Oncology, West China Hospital of Stomatology
State Key Laboratory of Biotherapy
West China Hospital of Sichuan University
Tianfu Jincheng Laboratory
Laboratory of Neuro-System and Multimorbidity, West China Hospital
Guang’an People’s Hospital
Funding
Sichuan Provincial Science and Technology Support Program · Frontiers Medical Center, Tianfu Jincheng Laboratory · cross research project of West China Hospital