The conceptual design of pH responsive ZnO-adamantane nanosystems for insulin amyloidosis

• Published in: Colloids and surfaces. A, Physicochemical and engineering aspects Physicochemical and engineering aspects, 2024-09, Vol.697, p.134443, Article 134443
• Main Authors: Giannousi, Kleoniki, Kasapidou, Angeliki Virginia, Oikonomou, Ilias M., Karageorgou, Maria-Eleni, Komninou, Philomela, Dendrinou-Samara, Catherine
• Format: Article
• Language: English
• Subjects: Adamantane; Nanosystem; pH responsive; ZnO NPs
• ISSN: 0927-7757; 1873-4359
• DOI: 10.1016/j.colsurfa.2024.134443

Adamantane derivatives are already being explored in amyloidogenic diseases, while ZnO nanoparticles (NPs) have the potential for affecting amyloidosis. Herein, the transformation of ZnO NPs and adamantane-1-carboxylic acid (ADA) to advanced pH responsive nanosystems is reported. Primary ZnO NPs were isolated under a simple solvothermal self-assembly synthetic procedure in the sole presence of octadecylamine (ODA). By adjusting the reaction time (8–24 h), wurtzites of crystallite sizes 19, 21 and 23 nm, respectively, were synthesized with co-crystallized ODA in monoloayer or bilayer conformation. The NPs with the bilayer of ODA have been functionalized with ADA through an amide bond, while those with the ODA monolayer were further PEGylated and ADA was loaded. Loaded ADA-ZnO nanosystems affected insulin amyloidosis in acidic pH (4.8), both in terms of final aggregation status (40 %) and by retarding the lag phase of amyloids formation. The sustained release profile of ADA was confirmed, while interaction with calf thymus DNA (CT-DNA) was evidenced by hyperchromicity. The pH of 4.8 was not enough to cleave the peptide bond, and thus the direct conjugation of ADA was effective only in prolonging the lag phase, without affecting the final amyloid formation, giving rise to the inherent properties of ZnO, foregrounding a prodrug character. [Display omitted] •Coated ZnO NPs as the structural building blocks of pH responsive nanosystems.•Direct conjugation of adamantanes and/or loading into polyethylene glycol matrix.•pH responsive loaded ADA-ZnO nanosystems, affect insulin amyloidosis in acidic pH.•Sustained release of ADA via PEG swelling and hypochromicity in CT-DNA studies.•Nanosystems act as drugs or prodrugs depending on the post-functionalization method.