Acta Pharmaceutica Sinica B (Jul 2024)
Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors
- 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
Affiliations
- Saini Setua
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA
- Shabia Shabir
- Department of Computer Science, Islamic University of Science and Technology, Awantipora, J&K 192122, India
- Poornima Shaji
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Ana Martinez Bulnes
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Anupam Dhasmana
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA; Himalayan School of Biosciences and Cancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun 248016, India
- Swathi Holla
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Nivesh K. Mittal
- Plough Center for Sterile Drug Delivery Solutions, UTHSC, Memphis, TN 38104, USA
- Nirakar Sahoo
- Department of Biology, College of Sciences, UTRGV, McAllen, TX 78539, USA
- Tripti Saini
- Department of Biology, College of Sciences, UTRGV, McAllen, TX 78539, USA
- Francesco Giorgianni
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA
- Mohammad Sikander
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Andrew E. Massey
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD 20892, USA
- Bilal B. Hafeez
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Manish K. Tripathi
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Vincent P. Diego
- South Texas Diabetes and Obesity Institute, UTRGV, McAllen, TX 78504, USA
- Meena Jaggi
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Junming Yue
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA
- Nadeem Zafar
- Dept. of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA
- Murali M. Yallapu
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Stephen W. Behrman
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Surgery, Baptist Memorial Medical Education, Baptist Memorial Hospital, Memphis, TN 38120, USA; Baptist Health Sciences University, Memphis, TN 38104, USA; Corresponding authors.
- Sheema Khan
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA; Corresponding authors.
- Subhash C. Chauhan
- Department of Pharmaceutical Sciences, College of Pharmacy, and College of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, TN 36163, USA; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, the University of Texas Rio Grande Valley, McAllen, TX 78504, USA; Corresponding authors.
- Journal volume & issue
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Vol. 14,
no. 7
pp. 3009 – 3026
Abstract
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 cargo. This 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 ultrasound. Herein, 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 payloads. NAF-derived EXs (NAF-EXs) were used for loading ormeloxifene (ORM), a potent anti-cancer and desmoplasia inhibitor as a model drug. We 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 Ca2+ influx in fibroblast cells. NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition (EMT) and repressed tumor growth in xenograft mouse model. In 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 drugs. Additionally, it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.
