Vágvölgyi, Máté and Kocsis, Endre and Tayeb, Bizhar Ahmed and Zupkó, István and Minorics, Renáta and Martins, Ana and Hoyk, Zsófia and Ballai, Gergő and Szenti, Imre and Kónya, Zoltán and Gáti, Tamás and Bogdán, Dóra and Tóth, Gábor and Hunyadi, Attila (2025) Ecdysteroid-Containing Squalenoylated Self-Assembling Nanoparticles Exert Tumor-Selective Sensitization to Reactive Oxygen Species (ROS)-Induced Oxidative Damage While Protecting Normal Cells: Implications for Selective Radiotherapy. JOURNAL OF MEDICINAL CHEMISTRY, 68 (7). pp. 7197-7212. ISSN 0022-2623
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Abstract
Central nervous system (CNS) tumors are exceptionally difficult to treat, and oxidative stress-inducing radiotherapy is an important treatment modality. In this study, we examined self-assembling pro-drug nanoconjugates of naturally derived antitumor ecdysteroids, which were designed to interfere with oxidative stress in brain tumor cells. Eight ecdysteroid-squalene conjugates were semi-synthesized and formulated into self-assembled aqueous nanosuspensions, which showed excellent stability for up to 16 weeks. The nanoassemblies demonstrated a strong dose-dependent sensitizing effect to tert-butyl hydroperoxide (tBHP)-induced oxidative damage in SH-SY5Y cells, while exerting a strong protective effect in MRC-5 fibroblast cells. In contrast, free ecdysteroids protected both cell lines from tBHP-induced damage. This suggests an important role for squalenoylation in the antitumor effect and indicates that our conjugates have potential as highly selective adjuvants in radiotherapy by sensitizing cancer cells and protecting surrounding tissues. Furthermore, our findings suggest a potential neuroprotective effect of nonconjugated ecdysteroids.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: Nemzeti Kutat?si Fejleszt?si ?s Innov?ci?s Hivatal [K134704, TKP2021-EGA-32]; National Research, Development and Innovation Office, Hungary (NRDIO) [UNKP-23-4-222]; Ministry of Innovation and Technology; New National Excellence Program of the Ministry for Culture and Innovation from the Source of the NRDIO; National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation Funding text: This work was funded by the National Research, Development and Innovation Office, Hungary (NRDIO; K134704 and TKP2021-EGA-32) by the Ministry of Innovation and Technology. M.V. was supported by the UNKP-23-4-222 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the NRDIO. E. K. was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation. The authors are grateful to Dr. Rainer Haessner (Technical University of Munich, Munich, Germany) for taking the 950 MHz NMR spectra, and for Prof. Maria Deli (Biological Research Centre, Szeged, Hungary) for offering facilities to perform Western blot assays. |
| Subjects: | Q Science / természettudomány > QD Chemistry / kémia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 19 Mar 2026 14:28 |
| Last Modified: | 19 Mar 2026 14:28 |
| URI: | https://real.mtak.hu/id/eprint/235899 |
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