富含木犀草素-7-O-鲁蒂诺侧链的芦荟皮源纳米颗粒通过恢复FADS1介导的脂肪酸代谢，减轻皮肤光老化现象。

Abstract

Aloe rind nanoparticles outperform aloe gel nanoparticles against photoaging. • Luteolin-7-O-rutinoside is a key metabolite enriched in aloe rind nanoparticles. • Luteolin-7-O-rutinoside directly binds FADS1 and restores fatty acid metabolism. • L7R-engineered rADNPs show enhanced protection against UV-induced photoaging. Background Ultraviolet (UV) radiation causes skin photoaging by inducing reactive oxygen species (ROS) accumulation, extracellular matrix remodeling, and lipid metabolic dysregulation, which may progress to actinic keratosis and invasive squamous cell carcinoma. Plant-derived exosome-like nanoparticles (PDNPs) are promising anti-aging strategies, but current studies mainly focus on PDNPs-associated miRNAs, whereas the roles and targets of enriched secondary metabolites remain unclear. This study aimed to elucidate the key metabolite and mechanism underlying the anti-photoaging activity of aloe rind-derived nanoparticles (rADNPs). Methods Aloe gel-derived nanoparticles (gADNPs) were used as controls to evaluate rADNPs in UV-induced photoaging models. Widely targeted plant metabolomics and transcriptomics were integrated to characterize the metabolic fingerprint of rADNPs and identify metabolite-target interactions. Molecular docking, molecular dynamics simulations, gene knockdown, and targeted fatty acid metabolomics were further performed to validate the key regulatory axis. Luteolin-7-O-rutinoside-engineered rADNPs (L7R-rADNPs) were constructed and assessed in dermal fibroblasts and HaCaT cells. Results rADNPs showed stronger anti-photoaging effects than gADNPs. Integrated analyses identified luteolin-7-O-rutinoside (L7R) as a key enriched metabolite in rADNPs. Mechanistic analyses showed that L7R targeted fatty acid desaturase 1 (Fads1), restoring UV-induced polyunsaturated fatty acid (PUFAs) depletion, rebalancing fatty acid metabolism, and enhancing endogenous antioxidant defenses. L7R-rADNPs further enhanced protection against UV-induced oxi