AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance.
Animals
Disulfiram
/ pharmacology
Mice
Insulin Resistance
Liver
/ metabolism
Reactive Oxygen Species
/ metabolism
Male
Mice, Inbred C57BL
Diabetes Mellitus, Type 2
/ drug therapy
Porosity
Humans
Oxidative Stress
/ drug effects
Drug Delivery Systems
/ methods
Mice, Obese
Hepatocytes
/ metabolism
Diet, High-Fat
Blood Glucose
/ drug effects
Superoxide Dismutase
/ metabolism
Insulin
/ metabolism
Signal Transduction
/ drug effects
Disaccharides
Disulfiram
Insulin resistance
Nanozymes
Oxidative stress
Targeted drug delivery
Journal
Journal of nanobiotechnology
ISSN: 1477-3155
Titre abrégé: J Nanobiotechnology
Pays: England
ID NLM: 101152208
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
14
06
2024
accepted:
26
09
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous hollow cascade nanozymes (AuCePt PHNs) are designed by integrating the dominant enzymatic activities of three metallic materials, which exhibit superior superoxide dismutase/catalase-like activities, and high drug loading capacity. In vitro experiments proved that AuCePt PHNs can ultra-efficiently scavenge endogenous and exogenous ROS. Moreover, AuCePt PHNs modified with lactobionic acid (LA) and loaded with disulfiram (DSF), named as AuCePt PHNs-LA@DSF, can significantly improve glucose uptake and glycogen synthesis in IR hepatocytes by regulating the insulin signaling pathways (IRS-1/AKT) and gluconeogenesis signaling pathways (FOXO-1/PEPCK). Intravenous administration of AuCePt PHNs-LA@DSF not only showed high liver targeting efficiency, but also reduced body weight and blood glucose and improved IR and lipid accumulation in high-fat diet-induced obese mice and diabetic ob/ob mice. This research elucidates the intrinsic activity of AuCePt PHNs for cascade scavenging of ROS, and reveals the potential effect of AuCePt PHNs-LA@DSF in T2DM treatment.
Identifiants
pubmed: 39456019
doi: 10.1186/s12951-024-02880-z
pii: 10.1186/s12951-024-02880-z
doi:
Substances chimiques
Disulfiram
TR3MLJ1UAI
Reactive Oxygen Species
0
lactobionic acid
65R938S4DV
Blood Glucose
0
Superoxide Dismutase
EC 1.15.1.1
Insulin
0
Disaccharides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
660Subventions
Organisme : National Natural Science Foundation for the Youth of China
ID : 81902171
Organisme : Natural Science Foundation of Chongqing, China
ID : cstc2020jcyj-msxmX0040
Organisme : National Natural Science Foundation of China
ID : 82170816
Informations de copyright
© 2024. The Author(s).
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