ACS Central Science最新文献

筛选
英文 中文
Synergistic Antitumor Immunotherapy via Mitochondria Regulation in Macrophages and Tumor Cells by an Iridium Photosensitizer 铱光敏剂通过线粒体调控巨噬细胞和肿瘤细胞的协同抗肿瘤免疫治疗
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-11 DOI: 10.1021/acscentsci.4c0215610.1021/acscentsci.4c02156
Shumeng Li, Hao Yuan, Xiu-Zhi Yang, Xinyu Xu, Wenhao Yu, Yanping Wu, Shankun Yao, Jin Xie, Weijiang He, Zijian Guo* and Yuncong Chen*, 
{"title":"Synergistic Antitumor Immunotherapy via Mitochondria Regulation in Macrophages and Tumor Cells by an Iridium Photosensitizer","authors":"Shumeng Li,&nbsp;Hao Yuan,&nbsp;Xiu-Zhi Yang,&nbsp;Xinyu Xu,&nbsp;Wenhao Yu,&nbsp;Yanping Wu,&nbsp;Shankun Yao,&nbsp;Jin Xie,&nbsp;Weijiang He,&nbsp;Zijian Guo* and Yuncong Chen*,&nbsp;","doi":"10.1021/acscentsci.4c0215610.1021/acscentsci.4c02156","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02156https://doi.org/10.1021/acscentsci.4c02156","url":null,"abstract":"<p >Mitochondrial targeting has emerged as an attractive method for antitumor treatment. However, most of the mitochondria targeted drugs focused on inhibiting tumor cells, while their potential for activation of immune responses in the tumor microenvironment has rarely been described. In this study, we report a photosensitive iridium complex <b>MitoIrL2</b>, which enabled the simultaneous mitochondrial modulation of macrophages and tumor cells to achieve synergistic antitumor immunity. The adjustment of the mitochondrial respiratory chain, HIF-1α, and the NF-κB pathway in macrophages drove the metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis, converting protumor M2 into the antitumor M1 phenotype. Downregulated expression of immunosuppressive checkpoint SIRPα has also been observed on macrophages. Meanwhile, the mitochondrial targeting <b>MitoIrL2</b> enhanced the immunogenic cell death of tumor cells and reversed the immunosuppressive tumor microenvironment, which activated the systemic immune response and established long-term immune memory <i>in vivo</i>. This work illustrates a promising strategy to simultaneously regulate macrophages toward the antitumor phenotype and enhance immunogenic cell death in tumor cells for synergistic antitumor immunotherapy.</p><p >A mitochondrial targeting iridium photosensitizer could achieve direct immune activation of both macrophages and tumor cells, synergistically enhancing antitumor immunity via mitochondrial modulation.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"441–451 441–451"},"PeriodicalIF":12.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Researchers Face Challenges Devising a PFAS-Free Future. 研究人员面临设计无pfas未来的挑战。
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-11 eCollection Date: 2025-03-26 DOI: 10.1021/acscentsci.5c00389
XiaoZhi Lim
{"title":"Researchers Face Challenges Devising a PFAS-Free Future.","authors":"XiaoZhi Lim","doi":"10.1021/acscentsci.5c00389","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00389","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"371-375"},"PeriodicalIF":12.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Researchers Face Challenges Devising a PFAS-Free Future 研究人员面临设计无pfas未来的挑战
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-11 DOI: 10.1021/acscentsci.5c0038910.1021/acscentsci.5c00389
XiaoZhi Lim, 
{"title":"Researchers Face Challenges Devising a PFAS-Free Future","authors":"XiaoZhi Lim,&nbsp;","doi":"10.1021/acscentsci.5c0038910.1021/acscentsci.5c00389","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00389https://doi.org/10.1021/acscentsci.5c00389","url":null,"abstract":"<p >Academia and industry see mixed results replacing fluorinated chemicals in refrigeration, textiles, and ion-exchange membranes.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"371–375 371–375"},"PeriodicalIF":12.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic Antitumor Immunotherapy via Mitochondria Regulation in Macrophages and Tumor Cells by an Iridium Photosensitizer. 铱光敏剂通过线粒体调控巨噬细胞和肿瘤细胞的协同抗肿瘤免疫治疗。
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-11 eCollection Date: 2025-03-26 DOI: 10.1021/acscentsci.4c02156
Shumeng Li, Hao Yuan, Xiu-Zhi Yang, Xinyu Xu, Wenhao Yu, Yanping Wu, Shankun Yao, Jin Xie, Weijiang He, Zijian Guo, Yuncong Chen
{"title":"Synergistic Antitumor Immunotherapy via Mitochondria Regulation in Macrophages and Tumor Cells by an Iridium Photosensitizer.","authors":"Shumeng Li, Hao Yuan, Xiu-Zhi Yang, Xinyu Xu, Wenhao Yu, Yanping Wu, Shankun Yao, Jin Xie, Weijiang He, Zijian Guo, Yuncong Chen","doi":"10.1021/acscentsci.4c02156","DOIUrl":"10.1021/acscentsci.4c02156","url":null,"abstract":"<p><p>Mitochondrial targeting has emerged as an attractive method for antitumor treatment. However, most of the mitochondria targeted drugs focused on inhibiting tumor cells, while their potential for activation of immune responses in the tumor microenvironment has rarely been described. In this study, we report a photosensitive iridium complex <b>MitoIrL2</b>, which enabled the simultaneous mitochondrial modulation of macrophages and tumor cells to achieve synergistic antitumor immunity. The adjustment of the mitochondrial respiratory chain, HIF-1α, and the NF-κB pathway in macrophages drove the metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis, converting protumor M2 into the antitumor M1 phenotype. Downregulated expression of immunosuppressive checkpoint SIRPα has also been observed on macrophages. Meanwhile, the mitochondrial targeting <b>MitoIrL2</b> enhanced the immunogenic cell death of tumor cells and reversed the immunosuppressive tumor microenvironment, which activated the systemic immune response and established long-term immune memory <i>in vivo</i>. This work illustrates a promising strategy to simultaneously regulate macrophages toward the antitumor phenotype and enhance immunogenic cell death in tumor cells for synergistic antitumor immunotherapy.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"441-451"},"PeriodicalIF":12.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Promiscuity in Nature Extends to Central Protein Biosynthetic Machinery. 自然界的乱交延伸到中心蛋白质生物合成机制。
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-10 eCollection Date: 2025-03-26 DOI: 10.1021/acscentsci.5c00387
April L Lukowski
{"title":"Promiscuity in Nature Extends to Central Protein Biosynthetic Machinery.","authors":"April L Lukowski","doi":"10.1021/acscentsci.5c00387","DOIUrl":"10.1021/acscentsci.5c00387","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"379-381"},"PeriodicalIF":12.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Promiscuity in Nature Extends to Central Protein Biosynthetic Machinery 自然界的乱交延伸到中心蛋白质生物合成机制
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-10 DOI: 10.1021/acscentsci.5c0038710.1021/acscentsci.5c00387
April L. Lukowski​, 
{"title":"Promiscuity in Nature Extends to Central Protein Biosynthetic Machinery","authors":"April L. Lukowski​,&nbsp;","doi":"10.1021/acscentsci.5c0038710.1021/acscentsci.5c00387","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00387https://doi.org/10.1021/acscentsci.5c00387","url":null,"abstract":"<p >Thioesters, rather than oxo-esters, can be tolerated and processed during translation to incorporate unnatural monomers.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"379–381 379–381"},"PeriodicalIF":12.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diversity Scale of Library Matters: Impact of mRNA Library Diversity Scales on the Discovery of Macrocyclic Peptides Targeting a Protein by the RaPID System. 文库物质的多样性尺度:mRNA文库多样性尺度对快速系统发现靶向蛋白质的大环肽的影响
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-10 eCollection Date: 2025-03-26 DOI: 10.1021/acscentsci.4c01021
Jinxuan Zhao, Yi Li, Naohiro Terasaka, Haruo Aikawa, Hiroaki Suga
{"title":"Diversity Scale of Library Matters: Impact of mRNA Library Diversity Scales on the Discovery of Macrocyclic Peptides Targeting a Protein by the RaPID System.","authors":"Jinxuan Zhao, Yi Li, Naohiro Terasaka, Haruo Aikawa, Hiroaki Suga","doi":"10.1021/acscentsci.4c01021","DOIUrl":"10.1021/acscentsci.4c01021","url":null,"abstract":"<p><p>Macrocyclic peptides make up a unique class of modalities known for their high affinity, specificity, and ability to modulate protein-protein interactions, including receptor activation. Messenger RNA display, including the Random Nonstandard Peptides Integrated Discovery (RaPID) system, stands out in identifying target-specific macrocyclic peptides, producing potent binders with low to subnanomolar dissociation constants against diverse targets. It has often been discussed that this success is partly attributed to the vast library of over a trillion different peptide sequences expressed from the corresponding mRNA sequences. However, the impact of library scales on the identification of various binders has not been experimentally validated. Here, we report the RaPID selections against an ectodomain of a receptor tyrosine kinase MET using peptide libraries ranging from 10<sup>6</sup> to 10<sup>14</sup> unique members of mRNAs. We thoroughly analyzed the outcomes, including the binding kinetic properties, of the enriched peptide families. This study provides valuable guidelines for designing libraries with various numbers of sequences and selection conditions to enrich macrocyclic peptides with the desired characteristics.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"431-440"},"PeriodicalIF":12.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diversity Scale of Library Matters: Impact of mRNA Library Diversity Scales on the Discovery of Macrocyclic Peptides Targeting a Protein by the RaPID System 文库物质的多样性尺度:mRNA文库多样性尺度对快速系统发现靶向蛋白质的大环肽的影响
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-09 DOI: 10.1021/acscentsci.4c0102110.1021/acscentsci.4c01021
Jinxuan Zhao, Yi Li, Naohiro Terasaka, Haruo Aikawa and Hiroaki Suga*, 
{"title":"Diversity Scale of Library Matters: Impact of mRNA Library Diversity Scales on the Discovery of Macrocyclic Peptides Targeting a Protein by the RaPID System","authors":"Jinxuan Zhao,&nbsp;Yi Li,&nbsp;Naohiro Terasaka,&nbsp;Haruo Aikawa and Hiroaki Suga*,&nbsp;","doi":"10.1021/acscentsci.4c0102110.1021/acscentsci.4c01021","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01021https://doi.org/10.1021/acscentsci.4c01021","url":null,"abstract":"<p >Macrocyclic peptides make up a unique class of modalities known for their high affinity, specificity, and ability to modulate protein–protein interactions, including receptor activation. Messenger RNA display, including the Random Nonstandard Peptides Integrated Discovery (RaPID) system, stands out in identifying target-specific macrocyclic peptides, producing potent binders with low to subnanomolar dissociation constants against diverse targets. It has often been discussed that this success is partly attributed to the vast library of over a trillion different peptide sequences expressed from the corresponding mRNA sequences. However, the impact of library scales on the identification of various binders has not been experimentally validated. Here, we report the RaPID selections against an ectodomain of a receptor tyrosine kinase MET using peptide libraries ranging from 10<sup>6</sup> to 10<sup>14</sup> unique members of mRNAs. We thoroughly analyzed the outcomes, including the binding kinetic properties, of the enriched peptide families. This study provides valuable guidelines for designing libraries with various numbers of sequences and selection conditions to enrich macrocyclic peptides with the desired characteristics.</p><p >The initial sampling of the sequence space determines the evolution of the families by the RaPID selection pressure for slow dissociation rates.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"431–440 431–440"},"PeriodicalIF":12.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
COFs in the Game: Harvest Water to Sustain 游戏中的COFs:收集水来维持生命
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-07 DOI: 10.1021/acscentsci.5c0035710.1021/acscentsci.5c00357
Grace C. Thaggard,  and , Natalia B. Shustova​, 
{"title":"COFs in the Game: Harvest Water to Sustain","authors":"Grace C. Thaggard,&nbsp; and ,&nbsp;Natalia B. Shustova​,&nbsp;","doi":"10.1021/acscentsci.5c0035710.1021/acscentsci.5c00357","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00357https://doi.org/10.1021/acscentsci.5c00357","url":null,"abstract":"<p >Breakthrough covalent-organic frameworks can harvest water directly from air at record-low humidity, paving the way for clean drinking water in arid regions.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"653–655 653–655"},"PeriodicalIF":12.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
COFs in the Game: Harvest Water to Sustain. 游戏中的COFs:收集水来维持生命。
IF 12.7 1区 化学
ACS Central Science Pub Date : 2025-03-07 eCollection Date: 2025-05-28 DOI: 10.1021/acscentsci.5c00357
Grace C Thaggard, Natalia B Shustova
{"title":"COFs in the Game: Harvest Water to Sustain.","authors":"Grace C Thaggard, Natalia B Shustova","doi":"10.1021/acscentsci.5c00357","DOIUrl":"10.1021/acscentsci.5c00357","url":null,"abstract":"<p><p>Breakthrough covalent-organic frameworks can harvest water directly from air at record-low humidity, paving the way for clean drinking water in arid regions.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"653-655"},"PeriodicalIF":12.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信