Safe transportation and targeted destruction:Albumin encapsulated aggregation-induced emission photosensitizer nanoaggregate for tumor photodynamic therapy through mitochondria damage-triggered pyroptosis  

作　　者：Juanmei Cao Yong Qu Shaojie Zhu Jinshan Zhan Yiting Xu Yifan Jin Yuqing Wang Zhuoxia Li Chuxing Chai Xiangwei Wu Meng Gao Changzheng Huang Min Li 

机构地区：[1]Department of Dermatology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Department of Hepatobiliary Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [3]National Engineering Research Center for Tissue Restoration and Reconstruction,Key Laboratory of Biomedical Engineering of Guangdong Province,Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,Innovation Center for Tissue Restoration and Reconstruction,School of Materials Science and Engineering,South China University of Technology,Guangzhou,China [4]Central Laboratory,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [5]NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases,Key Laboratory of Xinjiang Endemic and Ethnic Diseases,Department of Hepatobiliary Surgery,The First Affiliated Hospital of Shihezi University,Shihezi University School of Medicine,Shihezi,China [6]Department of Dermatology,The First Affiliated Hospital of Shihezi University,Shihezi,China

出　　处：《Aggregate》2024年第6期379-391,共13页聚集体(英文)

基　　金：National Natural Science Foundation of China,Grant/Award Numbers:82172754,22175065,81972565,81874208;Xinjiang Production and Construction Corps,Grant/Award Number:2023ZD023。

摘　　要：Photodynamic therapy is a highly recommended alternative treatment for solid tumors,such as cutaneous or luminal tumors,in clinical practice.However,conventional photosensitizers(PSs)often induce undesirable phototoxic effects because of their normal tissue distribution and a reduction in antitumor effects resulting from aggregation-caused quenching effects.The present study developed a novel nanoformulated aggregation-induced emission(AIE)-characteristic PS,nab-TTVPHE,which is composed of human serum albumin as a carrier and TTVPHE as a therapeutic agent,as a more effective cancer treatment with lower phototoxic effects.Notably,the reactive oxygen species generated by TTVPHE were shielded by the nanoaggregate structure,and the photodynamic activity was after nanostructure dissociation.Nab-TTVPHE was actively internalized in tumor cells via secreted protein,acidic and rich in cysteine and released to form nanoaggregates.TTVPHE accumulated in mitochondria,where it triggered mitochondrial damage under light irradiation via its photodynamic activity and induced pyroptosis via the caspase-3/gasdermin E(GSDME)signaling pathway to kill tumor cells.Therefore,this nano-formulated AIE-characteristic PS provides an innovative strategy for cancer treatment with lower phototoxic effect and the ability to boost potential antitumor immunity via GSDME-mediated pyroptosis.

关 键 词：aggregation-induced emission gasdermin E mitochondria damage nanoparticle albumin-bound photodynamic therapy PYROPTOSIS 

分 类 号：R73[医药卫生—肿瘤]