摘要
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 vitrolvivo 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.
基金
This study was supported by China Postdoctoral Science Foundation(Nos.2017M620159 and 2019T120345)
National Natural Science Foundation of China(Nos.81772098 and 81801917),Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(No.20152227)
Cross Research Project of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(No.JYJC202009)
Shanghai Health Industry Clinical Research Special Project(No.20204Y0443)
Shanghai Municipal Key Clinical Specialty(shslczdzk00901)
Scientific Research Foundation of Shanghai Municipal Commission of Health and Family Planning(No.20154Y002).