Lithium‐Charged Gold Nanoparticles: A New Powerful Tool for Lithium Delivery and Modulation of Glycogen Synthase Kinase 3 Activity
"A Trojan Horse for Lithium Delivery". Lithium has important pharmacological applications, although its use is severely limited due to its narrow therapeutic window of administrable concentrations. This study presents a novel nanocarrier for this metal cation based on glutathione-stabilized gold nanoparticles (LiG-AuNPs), which enable targeted release of lithium. LiG-AuNPs are easily synthesized, with dimensions of ≈2 nm, with a lithium loading of 2 wt%. These particles show a tendency to aggregate and a narrow size distribution. Aggregates of LiG-AuNPs (a-LiG-AuNPs) are non-toxic to cells at concentrations lower than 2 mg mL<sup>-1</sup> and are rapidly internalized into cells, where they release lithium in the cytosol through cation exchange, effectively modulating Glycogen Synthase Kinase-3 (GSK-3β) activity, especially the β isoform. Administration of a-LiG-AuNPs in murine models increased the inhibitory phosphorylation of GSK-3β at Ser9. Intranasal administration of a-LiG-AuNPs modulated GSK-3β activity in the brain, particularly in the hippocampus, without significantly altering plasma lithium levels, even when the administration lasted several months. LiG-AuNPs thus represent a powerful tool for the targeted administration of lithium, enhancing its therapeutic effects in modulating GSK-3β. They have potential applications for treating illnesses depending on GSK-3β (hyper)activation, such as mood disorders, Alzheimer's disease, and viral infections.
Authors
- Irene Contento
- Salvatore Impemba (ORCID: https://orcid.org/0009-0005-3644-357X)
- Alfonso Grassi (ORCID: https://orcid.org/0000-0002-2664-3114)
- Roberto Piacentini (ORCID: https://orcid.org/0000-0003-4215-1643)
- Martina Albini (ORCID: https://orcid.org/0000-0001-5671-2742)
- Maria Elena Marcocci (ORCID: https://orcid.org/0000-0003-4751-4263)
- Patrizia Canton (ORCID: https://orcid.org/0000-0003-1604-5265)
- Carmine Capacchione (ORCID: https://orcid.org/0000-0001-7254-8620)
- Claudio Grassi (ORCID: https://orcid.org/0000-0001-7253-1685)
- Francesco Pastore (ORCID: https://orcid.org/0000-0003-0064-1505)
- Antonio Buonerba (ORCID: https://orcid.org/0000-0003-1101-3248)
- Giulia Puliatti (ORCID: https://orcid.org/0000-0002-9275-4576)
- Mariarosa Scognamiglio (ORCID: https://orcid.org/0000-0002-1923-6844)
- Bruno Bandiera (ORCID: https://orcid.org/0000-0002-8311-7241)
- Silvia Baroni (ORCID: https://orcid.org/0009-0009-8528-7533)
- Domenica Donatella Li Puma (ORCID: https://orcid.org/0000-0001-6729-6967)
- Vincenzo Naddeo (ORCID: https://orcid.org/0000-0002-3395-3276)
- Beatrice Cannata (ORCID: https://orcid.org/0009-0000-4158-0062)
- Rocco Di Girolamo (ORCID: https://orcid.org/0000-0001-8815-2997)
- Laura Sposito
- Nicolina Castagno
Institutions
- Università Cattolica del Sacro Cuore (IT)
- University of Salerno (IT)
- Ca' Foscari University of Venice (IT)
- Agostino Gemelli University Polyclinic (IT)
- Federico II University Hospital (IT)
- University of Naples Federico II (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Advanced Materials
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1002/adma.202513858
- Citations
- 4
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 7.27