Localized surface plasmon resonance improves transdermal photodynamic therapy of hypertrophic scars

Photodynamic therapy (PDT) is an emerging therapeutic strategy for hypertrophic scars (HS), which is heavily dependent on reactive oxygen species (ROS) generation. However, the unsatisfactory delivery and excitation of 5-aminolevulinic acid (ALA, a commercial photosensitizer in dermatology) result in an insufficient ROS generation, and thus limit the clinical application of PDT treating HS (HS-PDT). Consequently, sophisticated transdermal co-delivery nanoethosomes (named A/A-ES) with ALA and Au nanotriangles (AuNTs) in cores are prepared via an in-situ seed-mediated growth method, and then applied to improve HS-PDT through localized surface plasmon resonance (LSPR)-enhanced ROS generation. A/A-ES display a satisfactory performance in co-delivery in HS tissue with sufficient protoporphyrin IX production and LSPR effect in cytoplasm, which is beneficial for ALA excitation as well as ROS generation. In vitro/vivo studies reveal that A/A-ES significantly improve HS-PDT in promoting to fibroblast apoptosis and collagen remodeling through LSPR-enhanced ROS generation. Therefore, this study provides a feasible strategy that integrates transdermal delivery and LSPR to enable the beneficial effects of HS-PDT through boosting the delivery and excitation of ALA.