{"title":"利用酶双自组装技术开发 AIEgens 系金纳米粒子,实现癌症特异性光热疗法的放大","authors":"Jiayi Bian, Yingjie Xu, Minghao Sun, Zerui Ma, Hao Li, Changrui Sun, Fei Xiong, Xiaopeng Zhao, Wenjing Yao, Yue Chen, Yuanyuan Ma, Xikuang Yao, Shenghong Ju, Wenpei Fan","doi":"10.1021/acsnano.4c07403","DOIUrl":null,"url":null,"abstract":"Accurate imaging and precise treatment are critical to controlling the progression of pancreatic cancer. However, current approaches for pancreatic cancer theranostics suffer from limitations in tumor specificity and invasive surgery. Herein, a pancreatic cancer-specific phototheranostic modulator (AuHQ) dominated by aggregation-induced emission (AIE) luminogens-tethered gold nanoparticles is meticulously designed to facilitate prominent fluorescence-photoacoustic bimodal imaging-guided photothermal immunotherapy. Once reaching the pancreatic tumor microenvironment (TME), the peptide Ala-Gly-Phe-Ser-Leu-Pro-Ala-Gly-Cys (AGFSLPAGC) linkage within AuHQ can be specifically cleaved by the overexpressed enzyme Cathepsin E (CTSE), triggering the dual self-assembly of AuNPs and AIE luminogens. The aggregation of AuNPs mediated by enzymatic cleavage results in potentiated photothermal therapy (PTT) under near-infrared (NIR) laser irradiation, induced immunogenic cell death (ICD), and enhanced photoacoustic imaging. Simultaneously, AIE luminogen aggregates formed by hydrophobic interaction can generate AIE fluorescence, enabling real-time and specific fluorescence imaging of pancreatic cancer. Furthermore, coadministration of an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with AuHQ can address the limitations of PTT efficacy imposed by the immunosuppressive TME and leverage the synergistic potential to activate systemic antitumor immunity. Thus, this well-designed phototheranostic modulator AuHQ facilitates the intelligent enzymatic dual self-assembly of imaging and therapeutic agents, providing an efficient and precise approach for pancreatic cancer theranostics.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":null,"pages":null},"PeriodicalIF":15.8000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Engineering AIEgens-Tethered Gold Nanoparticles with Enzymatic Dual Self-Assembly for Amplified Cancer-Specific Phototheranostics\",\"authors\":\"Jiayi Bian, Yingjie Xu, Minghao Sun, Zerui Ma, Hao Li, Changrui Sun, Fei Xiong, Xiaopeng Zhao, Wenjing Yao, Yue Chen, Yuanyuan Ma, Xikuang Yao, Shenghong Ju, Wenpei Fan\",\"doi\":\"10.1021/acsnano.4c07403\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Accurate imaging and precise treatment are critical to controlling the progression of pancreatic cancer. However, current approaches for pancreatic cancer theranostics suffer from limitations in tumor specificity and invasive surgery. Herein, a pancreatic cancer-specific phototheranostic modulator (AuHQ) dominated by aggregation-induced emission (AIE) luminogens-tethered gold nanoparticles is meticulously designed to facilitate prominent fluorescence-photoacoustic bimodal imaging-guided photothermal immunotherapy. Once reaching the pancreatic tumor microenvironment (TME), the peptide Ala-Gly-Phe-Ser-Leu-Pro-Ala-Gly-Cys (AGFSLPAGC) linkage within AuHQ can be specifically cleaved by the overexpressed enzyme Cathepsin E (CTSE), triggering the dual self-assembly of AuNPs and AIE luminogens. The aggregation of AuNPs mediated by enzymatic cleavage results in potentiated photothermal therapy (PTT) under near-infrared (NIR) laser irradiation, induced immunogenic cell death (ICD), and enhanced photoacoustic imaging. Simultaneously, AIE luminogen aggregates formed by hydrophobic interaction can generate AIE fluorescence, enabling real-time and specific fluorescence imaging of pancreatic cancer. Furthermore, coadministration of an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with AuHQ can address the limitations of PTT efficacy imposed by the immunosuppressive TME and leverage the synergistic potential to activate systemic antitumor immunity. Thus, this well-designed phototheranostic modulator AuHQ facilitates the intelligent enzymatic dual self-assembly of imaging and therapeutic agents, providing an efficient and precise approach for pancreatic cancer theranostics.\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":15.8000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Nano\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1021/acsnano.4c07403\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.4c07403","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Engineering AIEgens-Tethered Gold Nanoparticles with Enzymatic Dual Self-Assembly for Amplified Cancer-Specific Phototheranostics
Accurate imaging and precise treatment are critical to controlling the progression of pancreatic cancer. However, current approaches for pancreatic cancer theranostics suffer from limitations in tumor specificity and invasive surgery. Herein, a pancreatic cancer-specific phototheranostic modulator (AuHQ) dominated by aggregation-induced emission (AIE) luminogens-tethered gold nanoparticles is meticulously designed to facilitate prominent fluorescence-photoacoustic bimodal imaging-guided photothermal immunotherapy. Once reaching the pancreatic tumor microenvironment (TME), the peptide Ala-Gly-Phe-Ser-Leu-Pro-Ala-Gly-Cys (AGFSLPAGC) linkage within AuHQ can be specifically cleaved by the overexpressed enzyme Cathepsin E (CTSE), triggering the dual self-assembly of AuNPs and AIE luminogens. The aggregation of AuNPs mediated by enzymatic cleavage results in potentiated photothermal therapy (PTT) under near-infrared (NIR) laser irradiation, induced immunogenic cell death (ICD), and enhanced photoacoustic imaging. Simultaneously, AIE luminogen aggregates formed by hydrophobic interaction can generate AIE fluorescence, enabling real-time and specific fluorescence imaging of pancreatic cancer. Furthermore, coadministration of an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with AuHQ can address the limitations of PTT efficacy imposed by the immunosuppressive TME and leverage the synergistic potential to activate systemic antitumor immunity. Thus, this well-designed phototheranostic modulator AuHQ facilitates the intelligent enzymatic dual self-assembly of imaging and therapeutic agents, providing an efficient and precise approach for pancreatic cancer theranostics.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.