Luteolin-7-O-rutinoside-enriched aloe vera rind-derived nanoparticles attenuate skin photoaging by restoring FADS1-mediated fatty acid metabolism

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 oxidative stress and photoaging phenotypes, with consistent validation in HaCaT cells. CONCLUSION: rADNPs attenuate skin photoaging by delivering L7R, which restores Fads1-mediated fatty acid metabolism and strengthens antioxidant defense. These findings reveal a metabolite-driven mechanism underlying rADNPs anti-photoaging activity and provide new insights into studies of PDNPs for disease intervention.