Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer

• Published in: Biomedicine & pharmacotherapy 2024-06, Vol.175, p.116668, Article 116668
• Main Authors: Shestovskaya, Maria V., Luss, Anna L., Bezborodova, Olga A., Kulikov, Pavel P., Antufrieva, Daria A., Plotnikova, Ekaterina A., Makarov, Valentin V., Yudin, Vladimir S., Pankratov, Andrey A., Keskinov, Anton A.
• Format: Article
• Language: English
• Subjects: Applied magnetic field; Colon cancer; Iron oxide nanoparticles; Radiation treatment; Radiosensitivity
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.116668

The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence. Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model. [Display omitted] •Iron oxide nanoparticles coated with heparin were synthesized (hIONPs).•When irradiating in vitro, hIONPs increase cell death in colon cancer cells, but not in non-tumor cells.•The use of iron oxide nanoparticles improves the potency at least of primary irradiation.•Magnetic guidance ensures delivery of magnetic particles to the tumor site and can provide pronounced antitumor effect.