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Article

Iron Oxide Nanoparticles Carrying 5-Fluorouracil in Combination with Magnetic Hyperthermia Induce Thrombogenic Collagen Fibers, Cellular Stress, and Immune Responses in Heterotopic Human Colon Cancer in Mice

1
Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, D-07740 Jena, Germany
2
Leibniz Institute on Aging Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany
3
Chemicell GmbH, Erseburgstrasse 22–23, 12103 Berlin, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Donatella Paolino, Ana Isabel Fraguas-Sánchez and Cristina Martin-Sabroso
Pharmaceutics 2021, 13(10), 1625; https://doi.org/10.3390/pharmaceutics13101625
Received: 13 August 2021 / Revised: 29 September 2021 / Accepted: 30 September 2021 / Published: 6 October 2021
(This article belongs to the Special Issue Targeted Nanotherapy in Cancer Disease)
In this study we looked for the main protein pathway regulators which were responsible for the therapeutic impact on colon cancers when combining magnetic hyperthermia with the chemotherapeutic agent 5-fluorouracil (5FU). To this end, chitosan-coated magnetic nanoparticles (MNP) functionalized with 5FU were intratumorally injected into subcutaneous human colon cancer xenografts (HT-29) in mice and exposed to an alternating magnetic field. A decreased tumor growth was found particularly for the combined thermo-chemotherapy vs. the corresponding monotherapies. By using computational analysis of the tumor proteome, we found upregulated functional pathway categories termed “cellular stress and injury”, “intracellular second messenger and nuclear receptor signaling”, “immune responses”, and “growth proliferation and development”. We predict TGF-beta, and other mediators, as important upstream regulators. In conclusion, our findings show that the combined thermo-chemotherapy induces thrombogenic collagen fibers which are able to impair tumor nutrient supply. Further on, we associate several responses to the recognition of damage associated molecular patterns (DAMPs) by phagocytic cells, which immigrate into the tumor area. The activation of some pathways associated with cell survival implies the necessity to conduct multiple therapy sessions in connection with a corresponding monitoring, which could possibly be performed on the base of the identified protein regulators. View Full-Text
Keywords: magnetic hyperthermia; thermal treatment; nanoparticles; colon cancer; DAMPs; thrombogenic collagen fibers; endocytosis signaling magnetic hyperthermia; thermal treatment; nanoparticles; colon cancer; DAMPs; thrombogenic collagen fibers; endocytosis signaling
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MDPI and ACS Style

Dabaghi, M.; Rasa, S.M.M.; Cirri, E.; Ori, A.; Neri, F.; Quaas, R.; Hilger, I. Iron Oxide Nanoparticles Carrying 5-Fluorouracil in Combination with Magnetic Hyperthermia Induce Thrombogenic Collagen Fibers, Cellular Stress, and Immune Responses in Heterotopic Human Colon Cancer in Mice. Pharmaceutics 2021, 13, 1625. https://doi.org/10.3390/pharmaceutics13101625

AMA Style

Dabaghi M, Rasa SMM, Cirri E, Ori A, Neri F, Quaas R, Hilger I. Iron Oxide Nanoparticles Carrying 5-Fluorouracil in Combination with Magnetic Hyperthermia Induce Thrombogenic Collagen Fibers, Cellular Stress, and Immune Responses in Heterotopic Human Colon Cancer in Mice. Pharmaceutics. 2021; 13(10):1625. https://doi.org/10.3390/pharmaceutics13101625

Chicago/Turabian Style

Dabaghi, Mohammad, Seyed M.M. Rasa, Emilio Cirri, Alessandro Ori, Francesco Neri, Rainer Quaas, and Ingrid Hilger. 2021. "Iron Oxide Nanoparticles Carrying 5-Fluorouracil in Combination with Magnetic Hyperthermia Induce Thrombogenic Collagen Fibers, Cellular Stress, and Immune Responses in Heterotopic Human Colon Cancer in Mice" Pharmaceutics 13, no. 10: 1625. https://doi.org/10.3390/pharmaceutics13101625

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