Functional Transdermal Nanoethosomes Enhance Photodynamic Therapy of Hypertrophic Scars via Self-Generating Oxygen

Photodynamic therapy (PDT) is a new therapeutic strategy for hypertrophic scars (HSs), and nanoethosomes (ES) have attracted considerable attention as an efficient transdermal delivery system for PDT ofHSs (HS-PDT). However, the delivery of photosensitizers and the hypoxic microenvironment of HSs limit HS-PDT efficacy. Consequently, functional transdermal ES (A/A-ES) that are loaded with the photosensitizer, 5-aminolevulinic acid (ALA), and immobilized nanoenzyme Au nanoclusters (ANCs) within the ES surface have been developed that exhibit superior co-delivery characteristics and produce catalase that enhances HS-PDT efficacy. The unique structure of A/A-ES enables them to co-deliver ALA and ANCs into the HS tissue and to efficiently decompose the endogenous hydrogen peroxide in the HS to generate oxygen. The findings from in vitro and in vivo experiments demonstrated that A/A-ES efficiently co-delivered ALA and ANCs into the HS tissue and that they improved the hypoxic microenvironment of the HS. Systematic assessments reveal that A/A-ES enhance HS-PDT efficacy and that they are highly effective at improving the morphology and promoting HS fibroblast apoptosis and the rearrangement of collagen. These works give rise to an effective treatment option for HSs that integrates the transdermal co-delivery of ALA and nanoenzymes, thereby enabling them to exert their respective beneficial effects, and they highlight the enhancement of HS-PDT efficacy via self- generating oxygen.