Lithium‐Charged Gold Nanoparticles: A New Powerful Tool for Lithium Delivery and Modulation of Glycogen Synthase Kinase 3 Activity
Abstract
Abstract “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 −1 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.
Article Details
Authors (21)
Antonio Buonerba
Department of Chemistry and Biology “A. Zambelli” University of Salerno Fisciano SA Italy
Giulia Puliatti
Domenica Donatella Li Puma
Department of Neuroscience Università Cattolica del Sacro Cuore Largo F. Vito 1 Rome 00168 Italy
Bruno Bandiera
Department of Neuroscience Università Cattolica del Sacro Cuore Largo F. Vito 1 Rome 00168 Italy
Beatrice Cannata
Department of Neuroscience Università Cattolica del Sacro Cuore Largo F. Vito 1 Rome 00168 Italy
Maria Elena Marcocci
Department of Public Health and Infectious Diseases Sapienza University of Rome Piazzale Aldo Moro 5 Rome 00185 Italy
Nicolina Castagno
Department of Chemistry and Biology <i>“Adolfo Zambelli”</i> University of Salerno Via Giovanni Paolo II Fisciano SA 84084 Italy
Irene Contento
Department of Chemistry and Biology <i>“Adolfo Zambelli”</i> University of Salerno Via Giovanni Paolo II Fisciano SA 84084 Italy
Salvatore Impemba
Department of Chemistry and Biology <i>“Adolfo Zambelli”</i> University of Salerno Via Giovanni Paolo II Fisciano SA 84084 Italy
Mariarosa Scognamiglio
Department of Industrial Engineering University of Salerno Via Giovanni Paolo II Fisciano SA 84084 Italy
Rocco Di Girolamo
Dipartimento di Scienze Chimiche Università di Napoli Federico II Complesso Monte S. Angelo, Via Cintia Napoli I‐80126 Italy
Vincenzo Naddeo
Department of Civil Engineering University of Salerno Via Giovanni Paolo II Fisciano SA 84084 Italy
Patrizia Canton
Carmine Capacchione
Department of Chemistry and Biology “A. Zambelli” University of Salerno Fisciano SA Italy
Laura Sposito
Department of Neuroscience Università Cattolica del Sacro Cuore Largo F. Vito 1 Rome 00168 Italy
Martina Albini
Department of Neuroscience Università Cattolica del Sacro Cuore Largo F. Vito 1 Rome 00168 Italy
Francesco Pastore
Department of Neuroscience Università Cattolica del Sacro Cuore Largo F. Vito 1 Rome 00168 Italy
Silvia Baroni
Fondazione Policlinico Universitario A. Gemelli IRCCS Largo A. Gemelli 8 Rome 00168 Italy
Alfonso Grassi
Department of Chemistry and Biology <i>“Adolfo Zambelli”</i> University of Salerno Via Giovanni Paolo II Fisciano SA 84084 Italy
Claudio Grassi
Roberto Piacentini