Squalene-Based Nano-Assemblies Improve the Pro-Autophagic Activity of Trehalose
Giulia Frapporti,
Eleonora Colombo,
Hazem Ahmed,
Giulia Assoni,
Laura Polito,
Pietro Randazzo,
Daniela Arosio,
Pierfausto Seneci,
Giovanni Piccoli
Affiliations
Giulia Frapporti
Department of Cellular, Computational and Integrative Biology (CIBIO), Via Sommarive 9, Povo, I-38123 Trento, Italy
Eleonora Colombo
Chemistry Department, Università Statale di Milano, Via Golgi 19, I-20133 Milan, Italy
Hazem Ahmed
Chemistry Department, Università Statale di Milano, Via Golgi 19, I-20133 Milan, Italy
Giulia Assoni
Department of Cellular, Computational and Integrative Biology (CIBIO), Via Sommarive 9, Povo, I-38123 Trento, Italy
Laura Polito
Istituto di Scienze e Tecnologie Chimiche (SCITEC) “Giulio Natta”, Consiglio Nazionale delle Ricerche (CNR), Via G. Fantoli 16/15, I-20138 Milan, Italy
Pietro Randazzo
Promidis srl, Via Olgettina 60, I-20132 Milan, Italy
Daniela Arosio
Istituto di Scienze e Tecnologie Chimiche (SCITEC) “Giulio Natta”, Consiglio Nazionale delle Ricerche (CNR), Via Golgi 19, I-20133 Milan, Italy
Pierfausto Seneci
Chemistry Department, Università Statale di Milano, Via Golgi 19, I-20133 Milan, Italy
Giovanni Piccoli
Department of Cellular, Computational and Integrative Biology (CIBIO), Via Sommarive 9, Povo, I-38123 Trento, Italy
The disaccharide trehalose is a well-established autophagy inducer, but its therapeutic application is severely hampered by its low potency and poor pharmacokinetic profile. Thus, we targeted the rational design and synthesis of trehalose-based small molecules and nano objects to overcome such issues. Among several rationally designed trehalose-centered putative autophagy inducers, we coupled trehalose via suitable spacers with known self-assembly inducer squalene to yield two nanolipid-trehalose conjugates. Squalene is known for its propensity, once linked to a bioactive compound, to assemble in aqueous media in controlled conditions, internalizing its payload and forming nanoassemblies with better pharmacokinetics. We assembled squalene conjugates to produce the corresponding nanoassemblies, characterized by a hydrodynamic diameter of 188 and 184 nm and a high stability in aqueous media as demonstrated by the measured Z-potential. Moreover, the nanoassemblies were characterized for their toxicity and capability to induce autophagy in vitro.