Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

Authors

Saini Setua, University of Tennessee Health Science Center
Poornima Devi Shaji, The University of Texas Rio Grande Valley
Ana Martinez Bulnes, The University of Texas Rio Grande Valley
Anupam Dhasmana, The University of Texas Rio Grande Valley
Swathi Holla, The University of Texas Rio Grande Valley
Nirakar Sahoo, The University of Texas Rio Grande Valley
Tripti Saini, The University of Texas Rio Grande Valley
Mohammed Sikander, The University of Texas Rio Grande Valley
Bilal B. Hafeez, The University of Texas Rio Grande Valley
Manish K. Tripathi, The University of Texas Rio Grande Valley
Vincent Diego, The University of Texas Rio Grande ValleyFollow
Meena Jaggi, The University of Texas Rio Grande Valley
Murali M. Yallapu, The University of Texas Rio Grande Valley
Sheema Khan, The University of Texas Rio Grande Valley
Subhash C. Chauhan, The University of Texas Rio Grande Valley

Document Type

Article

Publication Date

4-9-2024

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.

Comments

Under a Creative Commons license. http://creativecommons.org/licenses/by-nc-nd/4.0/

Recommended Citation

Setua, S., Shabir, S., Shaji, P., Bulnes, A. M., Dhasmana, A., Holla, S., ... & Chauhan, S. C. (2024). Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2024.04.003

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Acta Pharmaceutica Sinica B

DOI

10.1016/j.apsb.2024.04.003

Academic Level

faculty