2026 ECNP Congress

PS03-3141

Manganese ferrite nanoparticles trigger selective superoxide dismutase-related responses in neuronal models and rat cortex

Anna Haduch — E. Bromek, R. Pukło, A.C. Moreno Maldonado, P. Alastuey, G.F. Goya, W. Kuban · Maj Institute of Pharmacology- Polish Academy of Sciences, Department of Pharmacokinetics and Drug Metabolism, Krakow, Poland

2026 ECNP Congress

Background

Nanoparticles are moving from passive carriers to active therapeutic and theranostic platforms for neurodegenerative disorders, because their size, surface chemistry and cargo capacity can be engineered to address central nervous system delivery barriers [1,2]. Recent work with magnetic nanoparticles in tauopathy models further illustrates that such systems can be designed not only to deliver molecules, but also to engage disease-relevant mechanisms [3]. Since oxidative stress is a central component of Alzheimer’s disease and other neurodegenerative cascades [4], redox-active nanomaterials with enzyme-mimetic properties represent a particularly attractive, but still insufficiently validated, class of candidates. We asked whether manganese ferrite nanoparticles could provide such a biologically active, magnetically tractable scaffold.

Methods

Three magnetic nanoparticle formulations were compared: uncoated barium hexaferrite (B2Pa), polyethylene glycol-coated barium hexaferrite (B2Pa@PEG), and manganese ferrite (M35). Human SH-SY5Y cells, either undifferentiated or differentiated towards a neuron-like phenotype, were exposed to 0–250 µg/mL nanoparticles for 24, 48 and 96 h. Cytocompatibility was assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays. Apparent intrinsic superoxide dismutase (SOD)-related activity was tested in a cell-free WST-based assay. In a second in vitro experiment, SH-SY5Y cells were exposed to M35 for 96 h and total SOD-related signal was measured. In vivo, M35 was administered unilaterally into the rat frontal cortex; total SOD and catalase activities were then compared between the exposed and contralateral hemispheres using paired within-animal analyses.

Results

The formulations are separated into two stories. B2Pa@PEG was the most cytocompatible material, maintaining viability close to control levels with low membrane damage, whereas uncoated B2Pa showed reduced tolerance after prolonged exposure. M35 produced the strongest biological response. At the highest screening concentration, undifferentiated SH-SY5Y viability decreased to approximately 10–15% after 96 h, and differentiated cells showed increased lactate dehydrogenase release, reaching approximately 130–140% at 250 µg/mL after 24 h. This high-concentration liability also revealed a central translational clue: M35 is not inert, but biologically potent, implying that future development should identify the minimal active exposure rather than push maximal concentrations. Consistent with this interpretation, M35 was the only formulation showing a weak but reproducible cell-free SOD-related signal. In SH-SY5Y cells, 96 h M35 exposure produced a modest increase in total SOD-related signal without a simple concentration-response pattern. In rat frontal cortex, M35 significantly increased total SOD activity versus the matched contralateral hemisphere (613 ± 49 versus 469 ± 27 U/mL; approximately +31%; p = 0.001), whereas catalase activity remained largely unchanged.

Conclusions

PEG coating improved barium hexaferrite compatibility, but manganese ferrite uniquely linked material-intrinsic SOD-like signal, cellular redox response and an early in vivo SOD increase. The therapeutic opportunity is therefore not maximal exposure but controlled low-dose activity. M35 should be viewed not as a finished therapeutic nanoparticle, but as a redox-active magnetic backbone for low-dose, surface-engineered and potentially targetable neuroprotective nanomedicine [5].

Acknowledgements:Supported by the National Science Centre, Poland, under M-ERA.NET 3 Call 2023, grant no. 2023/05/Y/NZ5/00256.

References

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