Chemical Engineering Journal · Nov 2026
Nanotherapy rejuvenating mitochondria via SIRT1 ubiquitination suppression attenuates glucolipotoxicity and promotes diabetic bone regeneration
By Chen Y, Guo K, Wu X et al.
Diabetes mellitus (DM)-associated impairment of bone regeneration remains a major clinical challenge worldwide, largely due to abnormal glucolipotoxicity, disruption of mineral microenvironment, and excessive accumulation of reactive oxygen species. Based on sequencing analysis of DM patients online databases and the Gene Expression Omnibus, mitochondrial energy metabolism may be implicated in the underlying mechanism. Herein, the mitochondrial rejuvenation-oriented nanotherapy using Au₇ nanoclusters (Au₇ NCs) via the one-pot self-assembly strategy was established, which exhibit great atomic precision, intrinsic photoluminescence, excellent biocompatibility and time-dependent reduction in local gold retention while simultaneously inhibiting senescence associated secretory phenotypes, restoring mitochondrial homeostasis and modulating bone metabolism balance to promote diabetic bone regeneration. Mechanistically, Au₇ NCs co-localize with silent information regulator 1 (SIRT1) in the perimitochondrial region and suppress its ubiquitin-mediated degradation. This effect alleviates cellular senescence and its deleterious downstream consequences, restores mitochondrial structure and function, and thereby re-establishes bone homeostasis. Moreover, Au₇ NCs effectively rescue drill-induced calvarial defects in vivo by orchestrating the balance between osteogenic and osteoclastic differentiation and inhibiting SIRT1 ubiquitination. Collectively, this study presents an Au₇ NCs-based nanotherapeutic platform capable of rejuvenating senescence cells and bidirectionally regulating bone remodeling, offering a novel tool for the underlying mechanism and a promising therapy for pathological bone injuries.