Young Chul Yoon, Dosang Lee, Jung Hyun Park, Ok-Hee Kim, Ho Joong Choi, Say-June Kim
{"title":"通过CD133-外泌体靶向递送PD-L1 siRNA加强胰腺癌治疗:临床前研究。","authors":"Young Chul Yoon, Dosang Lee, Jung Hyun Park, Ok-Hee Kim, Ho Joong Choi, Say-June Kim","doi":"10.1097/MPA.0000000000002419","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>This study assessed the anticancer potential of genetically modified exosomes engineered to express CD133-binding peptides on their surface and carry PD-L1 siRNA for the treatment of murine model of metastatic pancreatic cancer.</p><p><strong>Methods: </strong>CD133-targeting exosomes (tEx) were generated by harvesting conditioned media from adipose-derived stem cells (ASCs) that had undergone transformation using pDisplay vectors encoding CD133-binding peptide sequences. Subsequently, siPD-L1-loaded CD133-targeting Exosomes, referred to as tEx(s), were created by incorporating PD-L1 siRNA into the tEx using Exofect kit.</p><p><strong>Results: </strong>tEx(s) demonstrated superior targetability compared to other materials, including Ex, Ex(p), and tEx. This was substantiated by higher Total Radiant Efficiency (TRE) observed in metastatic liver and pancreatic tissues following intravenous administration of tEx(s) ( P < 0.05). Furthermore, the intravenous delivery of tEx(s) resulted in the most pronounced upregulation of pro-apoptotic markers (BIM and c-caspase 3) and the least downregulation of the anti-apoptotic markers (Mcl-1 and Bcl-xL) which has been demonstrated in various methods, including RT-PCR, Western blot analysis, and immunohistochemistry in the metastatic lesions in the livers ( P < 0.05).</p><p><strong>Conclusions: </strong>PD-L1 siRNA-loaded CD133-targeting exosomes demonstrated remarkable anticancer efficacy, characterized by specific binding to CD133-positive pancreatic cancer cells and suppression of PD-L1 expression within these cells.</p>","PeriodicalId":19733,"journal":{"name":"Pancreas","volume":" ","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhancing Pancreatic Cancer Therapy with Targeted CD133-Exosome Delivery of PD-L1 siRNA: A Preclinical Investigation.\",\"authors\":\"Young Chul Yoon, Dosang Lee, Jung Hyun Park, Ok-Hee Kim, Ho Joong Choi, Say-June Kim\",\"doi\":\"10.1097/MPA.0000000000002419\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>This study assessed the anticancer potential of genetically modified exosomes engineered to express CD133-binding peptides on their surface and carry PD-L1 siRNA for the treatment of murine model of metastatic pancreatic cancer.</p><p><strong>Methods: </strong>CD133-targeting exosomes (tEx) were generated by harvesting conditioned media from adipose-derived stem cells (ASCs) that had undergone transformation using pDisplay vectors encoding CD133-binding peptide sequences. Subsequently, siPD-L1-loaded CD133-targeting Exosomes, referred to as tEx(s), were created by incorporating PD-L1 siRNA into the tEx using Exofect kit.</p><p><strong>Results: </strong>tEx(s) demonstrated superior targetability compared to other materials, including Ex, Ex(p), and tEx. This was substantiated by higher Total Radiant Efficiency (TRE) observed in metastatic liver and pancreatic tissues following intravenous administration of tEx(s) ( P < 0.05). Furthermore, the intravenous delivery of tEx(s) resulted in the most pronounced upregulation of pro-apoptotic markers (BIM and c-caspase 3) and the least downregulation of the anti-apoptotic markers (Mcl-1 and Bcl-xL) which has been demonstrated in various methods, including RT-PCR, Western blot analysis, and immunohistochemistry in the metastatic lesions in the livers ( P < 0.05).</p><p><strong>Conclusions: </strong>PD-L1 siRNA-loaded CD133-targeting exosomes demonstrated remarkable anticancer efficacy, characterized by specific binding to CD133-positive pancreatic cancer cells and suppression of PD-L1 expression within these cells.</p>\",\"PeriodicalId\":19733,\"journal\":{\"name\":\"Pancreas\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-12-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pancreas\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/MPA.0000000000002419\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pancreas","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MPA.0000000000002419","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Enhancing Pancreatic Cancer Therapy with Targeted CD133-Exosome Delivery of PD-L1 siRNA: A Preclinical Investigation.
Objectives: This study assessed the anticancer potential of genetically modified exosomes engineered to express CD133-binding peptides on their surface and carry PD-L1 siRNA for the treatment of murine model of metastatic pancreatic cancer.
Methods: CD133-targeting exosomes (tEx) were generated by harvesting conditioned media from adipose-derived stem cells (ASCs) that had undergone transformation using pDisplay vectors encoding CD133-binding peptide sequences. Subsequently, siPD-L1-loaded CD133-targeting Exosomes, referred to as tEx(s), were created by incorporating PD-L1 siRNA into the tEx using Exofect kit.
Results: tEx(s) demonstrated superior targetability compared to other materials, including Ex, Ex(p), and tEx. This was substantiated by higher Total Radiant Efficiency (TRE) observed in metastatic liver and pancreatic tissues following intravenous administration of tEx(s) ( P < 0.05). Furthermore, the intravenous delivery of tEx(s) resulted in the most pronounced upregulation of pro-apoptotic markers (BIM and c-caspase 3) and the least downregulation of the anti-apoptotic markers (Mcl-1 and Bcl-xL) which has been demonstrated in various methods, including RT-PCR, Western blot analysis, and immunohistochemistry in the metastatic lesions in the livers ( P < 0.05).
Conclusions: PD-L1 siRNA-loaded CD133-targeting exosomes demonstrated remarkable anticancer efficacy, characterized by specific binding to CD133-positive pancreatic cancer cells and suppression of PD-L1 expression within these cells.
期刊介绍:
Pancreas provides a central forum for communication of original works involving both basic and clinical research on the exocrine and endocrine pancreas and their interrelationships and consequences in disease states. This multidisciplinary, international journal covers the whole spectrum of basic sciences, etiology, prevention, pathophysiology, diagnosis, and surgical and medical management of pancreatic diseases, including cancer.