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Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

Acta Pharmaceutica Sinica B 2024年第7期14卷 3009-3026页

作者： Saini Setua Shabia Shabir Poornima Shaji ana martinez bulnes Anupam Dhasmana Swathi Holla Nivesh K.Mittal Nirakar Sahoo Tripti Saini Francesco Giorgianni Mohammad Sikander Andrew E.Massey Bilal B.Hafeez Manish K.Tripathi Vincent P.Diego Meena Jaggi Junming Yue Nadeem Zafar Murali M.Yallapu Stephen W.Behrman Sheema Khan Subhash C.Chauhan Department of Pharmaceutical Sciences College of Pharmacyand College of MedicineUniversity of Tennessee Health Science Center(UTHSC)MemphisTN 36163USA Department of Computer Science Islamic University of Science and TechnologyAwantiporaJ&K 192122India Department of Immunology and Microbiology School of MedicineUniversity of Texas Rio Grande ValleyMcAllenTX 78504USA South Texas Center of Excellence in Cancer Research School of Medicinethe University of Texas Rio Grande ValleyMcAllenTX 78504USA Himalayan School of Biosciences and Cancer Research Institute Himalayan Institute of Medical SciencesSwami Rama Himalayan UniversityDehradun 248016India Plough Center for Sterile Drug Delivery Solutions UTHSCMemphisTN 38104USA Department of Biology College of SciencesUTRGVMcAllenTX 78539USA National Institute of Biomedical Imaging and Bioengineering(NIBIB) National Institutes of HealthBethesdaMD 20892USA South Texas Diabetes and Obesity Institute UTRGVMcAllenTX 78504USA Dept.of Laboratory Medicine&Pathology University of WashingtonSeattleWA 98195USA Department of Surgery Baptist Memorial Medical EducationBaptist Memorial HospitalMemphisTN 38120USA Baptist Health Sciences University MemphisTN 38104USA

The application of extracellular vesicles,particularly exosomes(EXs),is rapidly expanding in the field of medicine,owing to their remarkable properties as natural carriers of biological *** study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues(NAF-EXs)for personalized medicine,which can be derived at the time of diagnosis by endoscopic ***,we show that exosomes(EXs)derived from NAFs demonstrate differential bio-physical characteristics,efficient cellular internalization,drug loading efficiency,pancreatic tumor targeting and delivery of ***-derived EXs(NAF-EXs)were used for loading ormeloxifene(ORM),a potent anti-cancer and desmoplasia inhibitor as a model *** found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype,which may be due to regulation of Ca^(2+) influx in fibroblast ***-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition(EMT)and repressed tumor growth in xenograft mouse *** conclusion,our data suggests preferential tropism of NAF-EXs for PDAC tumors,thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer ***,it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

关键词： Pancreatic cancer Tumor adjacent normal tissue fibroblasts(NAF) Desmoplasia Extracellular vesicles Exosomes Tumor targeting Ormeloxifene Personalized medicine

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