Engineering Multifunctional Thylakoid as an Oxygen Self-Supplying Photosensitizer for Esophageal Squamous Cell Carcinoma-Targeted Photodynamic Therapy  

作　　者：Yingqiu Qi Hui Wang Anni Du Chen Liu Xiaofan Sun Xiaocao Meng Jinxiu Shen Sai-Yang Zhang Li-Rong Zhang Bing Jiang Guangjun Nie Huan Min 

机构地区：[1]Department of Pharmacology,School of Basic Medical Sciences,State Key Laboratory of Esophageal Cancer Prevention and Treatment,Nanozyme Medical Center,Zhengzhou University,Zhengzhou 450001 [2]Henan Institute of Advanced Technology,Zhengzhou University,Zhengzhou 450001 [3]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience,National Center for Nanoscience and Technology of China,Zhongguancun,Beijing 100190

出　　处：《CCS Chemistry》2023年第11期2519-2533,共15页中国化学会会刊（英文）

基　　金：supported by grants from the National Basic Research Plan of China(grant no.2018YFA0208900);the National Natural Science Foundation of China(grant nos.32000998,32000996,,U2004123);The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(grant no.2022HYTP046);the China Postdoctoral Science Foundation(grant nos.2019TQ0285,2019M662513,2020M682358,2020TQ0280,2021TQ0298).

摘　　要：Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.

关 键 词：esophageal squamous cell carcinoma THYLAKOID tumor targeting photodynamic therapy 

分 类 号：R73[医药卫生—肿瘤]