Engineered Capsaicin Delivery Systems for Immunogenic Cell Death Induction in Osteosarcoma: A Biomedical Engineering Perspective

Authors

  • Nafiseh Shayan fard Electronic department, semnan university, semnan, iran
  • Mohammad Shams PayZistAfzar Company, Tehran, Iran

DOI:

https://doi.org/10.5281/zenodo.16018597

Keywords:

Capsaicin, Calreticulin (CRT) Translocation, Immunogenic Cell Death (ICD), Drug delivery systems, Tumor microenvironment

Abstract

Osteosarcoma, the most common pediatric bone tumor, remains challenging to treat due to limited therapeutic advances. This study demonstrates capsaicin's dual anti-tumor effects in MG-63 osteosarcoma cells: direct cytotoxicity and immunogenic cell death (ICD) induction. Capsaicin triggered significant calreticulin (CRT) surface exposure (5.8-fold increase, p<0.01), enhancing dendritic cell phagocytosis by 3.5-fold compared to cisplatin-treated cells. Subsequent T-cell activation showed Th1-polarized immunity with elevated IFN-γ (320 pg/mL) without IL-4 increase. These findings position capsaicin as a promising natural ICD inducer for osteosarcoma therapy, warranting further preclinical development.

References

Anderson, M. E. (2019). Update on survival in osteosarcoma. Orthopedic Clinics, 50(3), 283-292.

Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., ... & Zitvogel, L. (2007). Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature Medicine, 13(9), 1050-1059.

Clark, R., & Lee, S. H. (2016). Anticancer properties of capsaicin against human cancer. Anticancer Research, 36(3), 837-843.

Ehsan Kianfar, M., Javanbakht, M., & Mirani, A. (2024). Absorption of heavy metal ions using chitosan/graphene nanocomposites. Journal of Environmental Nanotechnology, 12(2), 45-62.

Ghiringhelli, F., Apetoh, L., Tesniere, A., Aymeric, L., Ma, Y., Ortiz, C., ... & Zitvogel, L. (2009). Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nature Medicine, 15(10), 1170-1178.

Isakoff, M. S., Bielack, S. S., Meltzer, P., & Gorlick, R. (2015). Osteosarcoma: Current treatment and a collaborative pathway to success. Journal of Clinical Oncology, 33(27), 3029.

Jafari, R., Abdi, H., & Mirani, A. (2023). Computational modeling of chemoresistance in osteosarcoma stem cells. Journal of Biomechanical Engineering, 145(6), 061005.

Kianfar, E., & Mirani, A. (2024). Latest advances in application of liposomes and nanoliposomes. Nanotechnology Reviews, 13(1), 20240015.

Lau, J. K., Brown, K. C., Dom, A. M., Witte, T. R., Thornhill, B. A., Crabtree, C. M., ... & Dasgupta, P. (2014). Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway. Apoptosis, 19(8), 1190-1201.

Mirani, A. (2014). Diagnosis of skeletal malocclusion using facial electromyography signal analysis. Iranian Journal of Oral and Maxillofacial Radiology, 12(3), 45-53.

Mirani, A. (2024). Cover letter: Converging technologies in medical engineering. Medico & Engineering Future, 1(1), 1-3.

Obeid, M., Tesniere, A., Ghiringhelli, F., Fimia, G. M., Apetoh, L., Perfettini, J. L., ... & Zitvogel, L. (2007). Calreticulin exposure dictates the immunogenicity of cancer cell death. Nature Medicine, 13(1), 54-61.

Pommier, Y., Sun, Y., Huang, S. N., & Nitiss, J. L. (2018). Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nature Reviews Molecular Cell Biology, 17(11), 703-721.

Rein, M. J., Renouf, M., Cruz-Hernandez, C., Actis-Goretta, L., Thakkar, S. K., & da Silva Pinto, M. (2013). Bioavailability of bioactive food compounds: A challenging journey to bioefficacy. British Journal of Clinical Pharmacology, 75(3), 588-602.

Shen, S., Wu, Y., Liu, Y., & Wu, D. (2017). High drug-loading nanomedicines: Progress, current status, and prospects. International Journal of Nanomedicine, 12, 4085.

Zhou, W., Ke, S. Q., & Huang, Z. (2020). Translational regulation of the immune microenvironment in osteosarcoma. Advances in Experimental Medicine and Biology, 1258, 85-108.

Abdi, H., Mirani, A., & Jafari, R. (2024). Quantitative assessment of traumatic brain injury risk in diverse age groups of females: Insights from computational biomechanics. Heliyon, 10(10), e31542.

Branch, G., & Branch, S. T. (2024). Electrospun ZnO and GSH co-loaded PU/CS nanofibrous films as potential antibacterial wound dressings. World Journal of Nano Science and Engineering, 16, 2450028.

Garg, A. D., More, S., Rufo, N., Mece, O., Sassano, M. L., Agostinis, P., & Zitvogel, L. (2017). Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics. Oncoimmunology, 6(12), e1386829.

Jin, J., Lin, G., Huang, H., Xu, D., Yu, H., Ma, X., ... & Ma, D. (2016). Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53. International Journal of Biological Sciences, 12(5), 569.

Mirani, A., Maleknia, L., & Amirabadi, A. (2022). Preparation of bio-sensor with hybrid nanofibers of chitosan/functional carbon nanotubes for the sensing of nicotine. Journal of Color Science and Technology, 15(4), 271-286.

Mahmoud, Z. H., Hussein, U. A. R., Aljbory, N., Alnajar, M. J., Maleknia, L., & Mirani, A. (2025). Development of Vitex-derived polymer nanofibers using electrochemical sensors for the treatment of polycystic ovarian syndrome in rats as an animal model. Biosensors and Bioelectronics: X, 22, 100570.

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Published

2025-07-15

How to Cite

Shayan fard, N., & Shams, M. (2025). Engineered Capsaicin Delivery Systems for Immunogenic Cell Death Induction in Osteosarcoma: A Biomedical Engineering Perspective. MEDICO&ENGINEERING FUTURE, 2(1), 2–9. https://doi.org/10.5281/zenodo.16018597