A Mechanism Underpinning the Bioenergetic Metabolism-Regulating Function of Gold Nanocatalysts.

Autor: Wang Z; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA., Henriques A; Neuro-Sys, 410 D60, Gardanne, 13120, France., Rouvière L; Neuro-Sys, 410 D60, Gardanne, 13120, France., Callizot N; Neuro-Sys, 410 D60, Gardanne, 13120, France., Tan L; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA., Hotchkin MT; Clene Nanomedicine, Inc., Salt Lake City, UT, 84117, USA., Rossignol R; Cellomet, CARF Center, University of Bordeaux, 146 rue Léo Saignat, Bordeaux, 33000, France., Mortenson MG; Clene Nanomedicine, Inc., Salt Lake City, UT, 84117, USA.; Clene Nanomedicine, Inc., North East, MD, 21901, USA., Dorfman AR; Clene Nanomedicine, Inc., North East, MD, 21901, USA., Ho KS; Clene Nanomedicine, Inc., Salt Lake City, UT, 84117, USA., Wang H; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Feb; Vol. 20 (8), pp. e2304082. Date of Electronic Publication: 2023 Sep 28.
DOI: 10.1002/smll.202304082
Abstrakt: Bioenergetic deficits are known to be significant contributors to neurodegenerative diseases. Nevertheless, identifying safe and effective means to address intracellular bioenergetic deficits remains a significant challenge. This work provides mechanistic insights into the energy metabolism-regulating function of colloidal Au nanocrystals, referred to as CNM-Au8, that are synthesized electrochemically in the absence of surface-capping organic ligands. When neurons are subjected to excitotoxic stressors or toxic peptides, treatment of neurons with CNM-Au8 results in dose-dependent neuronal survival and neurite network preservation across multiple neuronal subtypes. CNM-Au8 efficiently catalyzes the conversion of an energetic cofactor, nicotinamide adenine dinucleotide hydride (NADH), into its oxidized counterpart (NAD + ), which promotes bioenergy production by regulating the intracellular level of adenosine triphosphate. Detailed kinetic measurements reveal that CNM-Au8-catalyzed NADH oxidation obeys Michaelis-Menten kinetics and exhibits pH-dependent kinetic profiles. Photoexcited charge carriers and photothermal effect, which result from optical excitations and decay of the plasmonic electron oscillations or the interband electronic transitions in CNM-Au8, are further harnessed as unique leverages to modulate reaction kinetics. As exemplified by this work, Au nanocrystals with deliberately tailored structures and surfactant-free clean surfaces hold great promise for developing next-generation therapeutic agents for neurodegenerative diseases.
(© 2023 The Authors. Small published by Wiley-VCH GmbH.)
Databáze: MEDLINE