Enhanced population of excited single state strategy:Irradiation and ultrasound dual-response and host tumor-driven nanosensitizers construction in triple synergistic therapy  

作　　者：Yaning Li Mengyan Tian Tianyue Yang Jiayu Cao Hongli Chen Jun Guo Pai Liu Yi Liu 

机构地区：[1]State Key Laboratory of Separation Membranes and Membrane Processes,School of Materials Science and Engineering,Tiangong University,Tianjin 300387,China [2]State Key Laboratory of Separation Membranes and Membrane Processes,School of Chemistry,Tiangong University,Tianjin 300387,China [3]State Key Laboratory of Separation Membranes and Membrane Processes,School of Life Science,Tiangong University,Tianjin 300387,China [4]State Key Laboratory of Separation Membrane and Membrane Process&Tianjin Key Laboratory of Green Chemical Technology and Process Engineering,School of Chemistry,Tiangong University,Tianjin 300387,China [5]School of Chemical and Environmental Engineering,Wuhan Polytechnic University,Wuhan 430023,China [6]Cangzhou Institute of Tiangong University,Cangzhou 061000,China

出　　处：《Nano Research》2024年第6期5501-5511,共11页纳米研究（英文版）

基　　金：the financial support from the National Natural Science Foundation of China(Nos.U23A2089,22205159,and 22103055);Natural Science Foundation of Tianjin(No.21JCQNJC01450);Science and Technology Plans of Tianjin(Nos.22ZYJDSS00070 and 21ZYJDJC00050).

摘　　要：Phototheranostics is an emerging field in synergistic antitumor therapy in which irradiation and sensitizers are combined to produce reactive oxygen species(ROS),bio-images,and high temperatures.All of these are arrived from the energy of sensitizers,which located in excited single state(S_(1)).Undeniably,the decentralization of the S_(1)population indirectly decreases the effect of each individual treatment.In this study,a strategy was proposed for enhancing the S_(1)population,and a sensitizer with mitochondrial targeting property,1,4-indolyl iodinated pyrrolo[3,2-b]pyrrole derivative(2I-TPIS),was assembled into adenosine triphosphate(ATP)-responsive nanoparticles(DPA-2I NPs)to achieve dual responses to irradiation and ultrasonication(US)for application to photo-sonodynamic therapy(PSDT).Compared with monotherapies,2I-TPIS generated more ROS in PSDT,inducing mitochondrial autophagy and apoptosis,which in turn triggered immunogenic cell death(ICD).Subsequently,DPA-2I NPs were constructed and self-assembled with the chemotherapeutic agents DPA-Cd and 2I-TPIS to achieve a triple synergistic strategy involving chemotherapy(CT)and PSDT.DPA-2I NPs exhibited absolute sensitization,intra-tumoral overexpression of ATP,and disassembly.Importantly,the biosafety and potent antitumor efficiency of the DPA-2I NP-based“PSDT+CT”therapy were revealed using a 4T1 tumor model.The study results provide insights into the design of sensitizers possessing a sufficient S_(1)population and a highly efficient tumor ablation capacity derived from molecular structural modulation,further enabling triple synergistic antitumor therapies,and expanding the clinical application of sensitizers.

关 键 词：triphosphate(ATP)-activated nano-sensitizers photo-sonodynamic therapy aggregation-induced emission enhanced excited state population 

分 类 号：R730.5[医药卫生—肿瘤]