Abstract

HighlightsWhat are the main findings?Chebulinic acid (CA), a bioactive polyphenol from Terminalia chebula, is confirmed to mitigate UVA-induced skin photoaging, expanding its anti-UVR damage application from UVB to UVA exposure.A membrane hybridization strategy is developed to repurpose non-PELN large particles (>1000 nm) into TAT-anchored extruded MELNs (eMELNs, ~200 nm), which effectively delivers CA across the skin barrier.What are the implications of the main findings?The TAT-anchored eMELN nanocarrier provides a green, biosafe and efficient transdermal delivery strategy by utilizing “waste” particles generated during PELN preparation, improving biological resource utilization.This study fills the gap in natural product-based UVA protection strategies, laying a foundation for developing next-generation natural anti-photoaging agents and promoting translational application of CA and PELNs in dermatology.Exposure to ultraviolet (UV), particularly UVA radiation, is a primary driver of photoaging due to its deep dermal penetration, which triggers DNA damage, collagen degradation, and immune suppression. Chebulinic acid (CA), a polyphenolic compound fromTerminalia chebula, exhibits potent antioxidant and anti-inflammatory properties against UVB-induced skin damage. However, its large molecular weight hinders transdermal delivery and the TAT47–57peptide (core of HIV-1 TAT) enables rapid transmembrane transport. Large particles with double-layer membrane structure and a diameter exceeding 1000 nm were obtained during the separation of plant-derived exosome-like nanoparticles (PELNs), which are not considered as PELNs (50–500 nm), after a mixture with TAT anchored to the surface of engineered artificial vesicles (EAVs) and extrusion causes membrane fusion, employed as novel nanocarriers to overcome the difficulty in skin penetration by leveraging their lipid bilayer structure and surface membrane-anchored TAT for efficient epidermal fusion and intercellular penetration