ZnO colludes with C. acnes in healing delay and Scar hyperplasia by barrier destruction.

As an important component of sunscreen products for sensitive skin, the potential damage mechanism of ZnO nanoparticles on skin surface with barrier structure or function defect caused by Cutibacterium acnes (C. acnes) has not been elucidated, which poses a serious challenge for reasonable selection of sunscreen products for acne-infected skin. In this work, we demonstrated for the first time that C. acnes induced significant changes in the membrane permeability and intracellular pH of fibroblasts through lipase up-regulation and lipid peroxidation, promoting endocytosis and ionization of ZnO NPs. High amounts of Zn^2 + further delayed acne wound healing and aggravated scar hyperplasia by intervening matrix metalloproteinase-9 (MMP-9) and TGF-β1/Smad pathway. MMP9 was confirmed to be the key target of ZnO in delaying acne wound healing by the wound regulatory effects of MMP9 agonist and MMP9 inhibitor. In summary, this work clarified the interaction mechanism between ZnO NPs and acne skins, providing guideline for the application of physical sunscreens for special skins.