Verteporfin-mediated on/off photoswitching functions synergistically to treat choroidal vascular diseases  

作　　者：Yahan Ju Xiaochan Dai Zhimin Tang Zunzhen Ming Ni Ni Dongqing Zhu Jing Zhang Bo Ma Jiajing Wang Rui Huang Siyu Zhao Yan Pang Ping Gu 

机构地区：[1]Department of Ophthalmology,Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,PR China [2]Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology,Shanghai,200011,PR China [3]Central Laboratory,Shanghai Tenth People’s Hospital,Tongji University,Shanghai,200072,PR China

出　　处：《Bioactive Materials》2022年第8期402-415,共14页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(81870687,82071004,32000972);the National Key R&D program of China(2018YFC1106100);the Key program of Shanghai Science and Technology Commission(19JC1415503);the Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20161316,20191820);Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(No.JYJC201907);Science and Technology Commission of Shanghai(20DZ2270800).

摘　　要：Choroidal vascular diseases,such as age-related macular degeneration,are the leading cause of vision impairment and are characterized by pathological angiogenesis.Verteporfin-mediated photodynamic therapy is a current strategy that selectively occludes choroidal neovasculature.However,the clinically used large-dose systemic administration increases the risk of systemic adverse events,such as phototoxicity to superficial tissues.In this study,we developed an in situ verteporfin delivery system with a photoswitching synergistic function that disassembles in response to intraocular inflammatory enzymes.Under light-on conditions,verteporfin-mediated photodynamic therapy effectively occurs and this leads to vascular occlusion.Under light-off conditions,non-photoactive verteporfin negatively regulates vascular endothelial growth factor-induced angiogenesis as a yes-associated protein inhibitor.Taken together,our system serves as an intraocular verteporfin reservoir to improve the bioavailability of verteporfin by innovatively exploiting its photochemical and biological functions.This work provides a promising strategy with synergistic antiangiogenic effects for the treatment of choroidal vascular diseases.

关 键 词：Pathological neovascularization Photodynamic therapy Bio-responsive release In situ drug delivery 

分 类 号：R318[医药卫生—生物医学工程]