ACS Central Science最新文献_第2页

Synergistic Antitumor Immunotherapy via Mitochondria Regulation in Macrophages and Tumor Cells by an Iridium Photosensitizer.

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":"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 MitoIrL2, 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 MitoIrL2 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 in vivo. 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.","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.

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

引用次数: 0

Promiscuity in Nature Extends to Central Protein Biosynthetic Machinery

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,

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.

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":"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 106 to 1014 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.","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

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, Yi Li, Naohiro Terasaka, Haruo Aikawa and Hiroaki Suga*, ","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":"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 106 to 1014 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.The initial sampling of the sequence space determines the evolution of the families by the RaPID selection pressure for slow dissociation rates.","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

Correction to "A Pair of Fluorescent Probes Enabling Precise Diagnosis of Liver Cancer by Complementary Imaging".

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-03-04 eCollection Date: 2025-03-26 DOI: 10.1021/acscentsci.5c00250

Min Gao, Sun Hyeok Lee, Haw-Young Kwon, Larissa Miasiro Ciaramicoli, Eunsol Jo, Young Hyun Yu, Fengming Li, Beomsue Kim, Kyungtae Hong, Jun-Seok Lee, Namhui Kim, Yoojin Oh, Chun Young Im, Chris Soon Heng Tan, Hyung-Ho Ha, Young-Tae Chang

引用次数: 0

Correction to “A Pair of Fluorescent Probes Enabling Precise Diagnosis of Liver Cancer by Complementary Imaging”

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-03-04 DOI: 10.1021/acscentsci.5c0025010.1021/acscentsci.5c00250

Min Gao*, Sun Hyeok Lee, Haw-Young Kwon, Larissa Miasiro Ciaramicoli, Eunsol Jo, Young Hyun Yu, Fengming Li, Beomsue Kim, Kyungtae Hong, Jun-Seok Lee, Namhui Kim, Yoojin Oh, Chun Young Im, Chris Soon Heng Tan*, Hyung-Ho Ha* and Young-Tae Chang*,

引用次数: 0

Automated Research Platform for Development of Triplet-Triplet Annihilation Photon Upconversion Systems.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-02-21 eCollection Date: 2025-03-26 DOI: 10.1021/acscentsci.4c02059

Paulius Baronas, Justas Lekavičius, Maciej Majdecki, Jacob Lynge Elholm, Karolis Kazlauskas, Przemysław Gaweł, Kasper Moth-Poulsen

{"title":"Automated Research Platform for Development of Triplet-Triplet Annihilation Photon Upconversion Systems.","authors":"Paulius Baronas, Justas Lekavičius, Maciej Majdecki, Jacob Lynge Elholm, Karolis Kazlauskas, Przemysław Gaweł, Kasper Moth-Poulsen","doi":"10.1021/acscentsci.4c02059","DOIUrl":"10.1021/acscentsci.4c02059","url":null,"abstract":"Triplet-triplet annihilation photon upconversion (TTA-UC) systems hold great promise for applications in energy, 3D printing, and photopharmacology. However, their optimization remains challenging due to the need for precise tuning of sensitizer and annihilator concentrations under oxygen-free conditions. This study presents an automated, high-throughput platform for the discovery and optimization of TTA-UC systems. Capable of performing 100 concentration scans in just two hours, the platform generates comprehensive concentration maps of critical parameters, including quantum yield, triplet energy transfer efficiency, and threshold intensity. Using this approach, we identify key loss mechanisms in both the established and novel TTA-UC systems. At high porphyrin-based sensitizer concentrations, upconversion quantum yield losses are attributed to sensitizer triplet self-quenching via aggregation and sensitizer triplet-triplet annihilation (sensitizer-TTA). Additionally, reverse triplet energy transfer (RTET) at elevated sensitizer levels increases the upconversion losses and excitation thresholds. Testing novel sensitizer-annihilator pairs confirms these loss mechanisms, highlighting opportunities for molecular design improvements. This automated platform offers a powerful tool for advancing TTA-UC research and other photochemical studies requiring low oxygen levels, intense laser excitation, and minimal material use.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"413-421"},"PeriodicalIF":12.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750191","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

Automated Research Platform for Development of Triplet–Triplet Annihilation Photon Upconversion Systems

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-02-21 DOI: 10.1021/acscentsci.4c0205910.1021/acscentsci.4c02059

Paulius Baronas, Justas Lekavičius, Maciej Majdecki, Jacob Lynge Elholm, Karolis Kazlauskas, Przemysław Gaweł and Kasper Moth-Poulsen*,

{"title":"Automated Research Platform for Development of Triplet–Triplet Annihilation Photon Upconversion Systems","authors":"Paulius Baronas, Justas Lekavičius, Maciej Majdecki, Jacob Lynge Elholm, Karolis Kazlauskas, Przemysław Gaweł and Kasper Moth-Poulsen*, ","doi":"10.1021/acscentsci.4c0205910.1021/acscentsci.4c02059","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02059https://doi.org/10.1021/acscentsci.4c02059","url":null,"abstract":"Triplet–triplet annihilation photon upconversion (TTA-UC) systems hold great promise for applications in energy, 3D printing, and photopharmacology. However, their optimization remains challenging due to the need for precise tuning of sensitizer and annihilator concentrations under oxygen-free conditions. This study presents an automated, high-throughput platform for the discovery and optimization of TTA-UC systems. Capable of performing 100 concentration scans in just two hours, the platform generates comprehensive concentration maps of critical parameters, including quantum yield, triplet energy transfer efficiency, and threshold intensity. Using this approach, we identify key loss mechanisms in both the established and novel TTA-UC systems. At high porphyrin-based sensitizer concentrations, upconversion quantum yield losses are attributed to sensitizer triplet self-quenching via aggregation and sensitizer triplet–triplet annihilation (sensitizer-TTA). Additionally, reverse triplet energy transfer (RTET) at elevated sensitizer levels increases the upconversion losses and excitation thresholds. Testing novel sensitizer–annihilator pairs confirms these loss mechanisms, highlighting opportunities for molecular design improvements. This automated platform offers a powerful tool for advancing TTA-UC research and other photochemical studies requiring low oxygen levels, intense laser excitation, and minimal material use.A high-throughput concentration screening method built from commercial components for determining upconversion quantum yield and excitation threshold in sensitized triplet−triplet annihilation systems.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"413–421 413–421"},"PeriodicalIF":12.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696364","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

How Does the Rate of Chain Exchange Relate to Stress Relaxation in Triblock Copolymer Networks?

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-02-20 DOI: 10.1021/acscentsci.4c0203110.1021/acscentsci.4c02031

Joanna M. White, Taehyoung Kim, Frank S. Bates* and Timothy P. Lodge*,

{"title":"How Does the Rate of Chain Exchange Relate to Stress Relaxation in Triblock Copolymer Networks?","authors":"Joanna M. White, Taehyoung Kim, Frank S. Bates* and Timothy P. Lodge*, ","doi":"10.1021/acscentsci.4c0203110.1021/acscentsci.4c02031","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02031https://doi.org/10.1021/acscentsci.4c02031","url":null,"abstract":"The relationship between macroscopic stress relaxation and molecular-level chain exchange in triblock copolymer micelles has been explored using rheology and time-resolved small-angle neutron scattering (TR-SANS), marking the first measurements of chain exchange in concentrated triblock networks. It has long been assumed in models of transient or thermoreversible networks that the time scales for these two processes are equal. Experimentally, we find that stress relaxation occurs many orders-of-magnitude faster than chain exchange. This difference is quantitatively explained by modest dispersity in the core block that results in a slight asymmetry within any given nominally symmetric triblock. For stress relaxation to occur, only the shorter chain must pull out, while chain exchange is slowed due to the requirement of the eventual pullout of the longer block. The pullout time is extremely sensitive to the length of the core block. This mechanism is supported by measurements with an intentionally asymmetric triblock copolymer, which displays an even larger difference between the stress relaxation and chain exchange rates. These results establish a quantitative molecular-level picture of the chain dynamics associated with stress relaxation in triblock copolymer networks.A quantitative relationship is established between the flow time of a BAB triblock copolymer network, from rheology, and the time for a single B end block to escape from its micellar cross-link, determined by neutron scattering.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 3","pages":"422–430 422–430"},"PeriodicalIF":12.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696363","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