ACS Central Science最新文献

{"title":"Hydrophilic Ethylene Glycol Fragments: A Determinant Affecting the Therapeutic Index of Paclitaxel Prodrug Nanoassemblies","authors":"Yaqi Li,&nbsp;Yixin Sun,&nbsp;Qing Wang,&nbsp;Shuo Wang,&nbsp;Cuiyun Liu,&nbsp;Yuetong Huang,&nbsp;Wenxin Zhong,&nbsp;Xiyan Wang,&nbsp;Wenjing Wang,&nbsp;Shiyi Zuo,&nbsp;Xianbao Shi,&nbsp;Xiaohui Pu,&nbsp;Jin Sun,&nbsp;Zhonggui He* and Bingjun Sun*,&nbsp;","doi":"10.1021/acscentsci.4c0100410.1021/acscentsci.4c01004","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01004https://doi.org/10.1021/acscentsci.4c01004","url":null,"abstract":"<p >Prodrug-based nanoassemblies are promising platforms for cancer therapy. Prodrugs typically consist of three main components: drug modules, intelligent response modules, and modification modules. However, the available modification modules are usually hydrophobic aliphatic side chains, which affect the activation efficiency of the prodrugs. Herein, hydrophilic ethylene glycol fragments were inserted between the modification modules and the response modules, and the important effects of hydrophilic fragments on the assembly, drug release, and therapeutic index of the prodrugs were investigated. Notably, the introduction of hydrophilic fragments affected the intermolecular forces of the prodrugs and increased the interaction of hydrogen bonding. In addition, hydrophilic fragments significantly improved the redox drug release profiles, which affected the therapeutic index of the prodrug nanoassemblies. PTX-SS-OA NPs with hydrophilic fragments exhibited increased redox sensitivity, enhanced cytotoxicity, and superior antitumor efficacy. In comparison, PTX-SS-OAL NPs without hydrophilic fragments showed limited redox sensitivity and cytotoxicity but displayed better safety. Overall, the hydrophilic fragment is a critical determinant in modulating the therapeutic index of the prodrug nanoassemblies, which contributes to the development of advanced prodrug nanodelivery systems.</p><p >Hydrophilic ethylene glycol fragment is a critical determinant in modulating the therapeutic index of the paclitaxel prodrug nanoassemblies.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2253–2265 2253–2265"},"PeriodicalIF":12.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143127461","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}

{"title":"Bespoke and Accessible Electrochemical Reactors","authors":"Charlotte E. Willans*,&nbsp;","doi":"10.1021/acscentsci.4c0179410.1021/acscentsci.4c01794","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01794https://doi.org/10.1021/acscentsci.4c01794","url":null,"abstract":"<p >User-friendly software that allows scientists to design, print, test, and iterate upon reactors enables key reactor parameters to be optimized for electrochemical reactions.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 11","pages":"2000–2002 2000–2002"},"PeriodicalIF":12.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142719498","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}

{"title":"Combination of Coevolutionary Information and Supervised Learning Enables Generation of Cyclic Peptide Inhibitors with Enhanced Potency from a Small Data Set","authors":"Ylenia Mazzocato,&nbsp;Nicola Frasson,&nbsp;Matthew Sample,&nbsp;Cristian Fregonese,&nbsp;Angela Pavan,&nbsp;Alberto Caregnato,&nbsp;Marta Simeoni,&nbsp;Alessandro Scarso,&nbsp;Laura Cendron,&nbsp;Petr Šulc and Alessandro Angelini*,&nbsp;","doi":"10.1021/acscentsci.4c0142810.1021/acscentsci.4c01428","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01428https://doi.org/10.1021/acscentsci.4c01428","url":null,"abstract":"<p >Computational generation of cyclic peptide inhibitors using machine learning models requires large size training data sets often difficult to generate experimentally. Here we demonstrated that sequential combination of Random Forest Regression with the pseudolikelihood maximization Direct Coupling Analysis method and Monte Carlo simulation can effectively enhance the design pipeline of cyclic peptide inhibitors of a tumor-associated protease even for small experimental data sets. Further <i>in vitro</i> studies showed that such <i>in silico</i>-evolved cyclic peptides are more potent than the best peptide inhibitors previously developed to this target. Crystal structure of the cyclic peptides in complex with the protease resembled those of protein complexes, with large interaction surfaces, constrained peptide backbones, and multiple inter- and intramolecular interactions, leading to good binding affinity and selectivity.</p><p >Combination of statistical and computational approaches enables rapid and cost-effective generation of potent cyclic peptide inhibitors of a human cancer associated protease.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2242–2252 2242–2252"},"PeriodicalIF":12.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143127460","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}

{"title":"Hydrophilic Ethylene Glycol Fragments: A Determinant Affecting the Therapeutic Index of Paclitaxel Prodrug Nanoassemblies.","authors":"Yaqi Li, Yixin Sun, Qing Wang, Shuo Wang, Cuiyun Liu, Yuetong Huang, Wenxin Zhong, Xiyan Wang, Wenjing Wang, Shiyi Zuo, Xianbao Shi, Xiaohui Pu, Jin Sun, Zhonggui He, Bingjun Sun","doi":"10.1021/acscentsci.4c01004","DOIUrl":"10.1021/acscentsci.4c01004","url":null,"abstract":"<p><p>Prodrug-based nanoassemblies are promising platforms for cancer therapy. Prodrugs typically consist of three main components: drug modules, intelligent response modules, and modification modules. However, the available modification modules are usually hydrophobic aliphatic side chains, which affect the activation efficiency of the prodrugs. Herein, hydrophilic ethylene glycol fragments were inserted between the modification modules and the response modules, and the important effects of hydrophilic fragments on the assembly, drug release, and therapeutic index of the prodrugs were investigated. Notably, the introduction of hydrophilic fragments affected the intermolecular forces of the prodrugs and increased the interaction of hydrogen bonding. In addition, hydrophilic fragments significantly improved the redox drug release profiles, which affected the therapeutic index of the prodrug nanoassemblies. PTX-SS-OA NPs with hydrophilic fragments exhibited increased redox sensitivity, enhanced cytotoxicity, and superior antitumor efficacy. In comparison, PTX-SS-OAL NPs without hydrophilic fragments showed limited redox sensitivity and cytotoxicity but displayed better safety. Overall, the hydrophilic fragment is a critical determinant in modulating the therapeutic index of the prodrug nanoassemblies, which contributes to the development of advanced prodrug nanodelivery systems.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2253-2265"},"PeriodicalIF":12.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902402","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}

{"title":"Bespoke and Accessible Electrochemical Reactors.","authors":"Charlotte E Willans","doi":"10.1021/acscentsci.4c01794","DOIUrl":"10.1021/acscentsci.4c01794","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 11","pages":"2000-2002"},"PeriodicalIF":12.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778722","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}

{"title":"Combination of Coevolutionary Information and Supervised Learning Enables Generation of Cyclic Peptide Inhibitors with Enhanced Potency from a Small Data Set.","authors":"Ylenia Mazzocato, Nicola Frasson, Matthew Sample, Cristian Fregonese, Angela Pavan, Alberto Caregnato, Marta Simeoni, Alessandro Scarso, Laura Cendron, Petr Šulc, Alessandro Angelini","doi":"10.1021/acscentsci.4c01428","DOIUrl":"10.1021/acscentsci.4c01428","url":null,"abstract":"<p><p>Computational generation of cyclic peptide inhibitors using machine learning models requires large size training data sets often difficult to generate experimentally. Here we demonstrated that sequential combination of Random Forest Regression with the pseudolikelihood maximization Direct Coupling Analysis method and Monte Carlo simulation can effectively enhance the design pipeline of cyclic peptide inhibitors of a tumor-associated protease even for small experimental data sets. Further <i>in vitro</i> studies showed that such <i>in silico</i>-evolved cyclic peptides are more potent than the best peptide inhibitors previously developed to this target. Crystal structure of the cyclic peptides in complex with the protease resembled those of protein complexes, with large interaction surfaces, constrained peptide backbones, and multiple inter- and intramolecular interactions, leading to good binding affinity and selectivity.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2242-2252"},"PeriodicalIF":12.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902389","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}

{"title":"Understanding Oxygen-Induced Reactions and Their Impact on n-Type Polymeric Mixed Conductor-Based Devices","authors":"Prem D. Nayak,&nbsp;Büsra Dereli,&nbsp;David Ohayon,&nbsp;Shofarul Wustoni,&nbsp;Tania Cecilia Hidalgo Castillo,&nbsp;Victor Druet,&nbsp;Yazhou Wang,&nbsp;Adel Hama,&nbsp;Craig Combe,&nbsp;Sophie Griggs,&nbsp;Maryam Alsufyani,&nbsp;Rajendar Sheelamanthula,&nbsp;Iain McCulloch,&nbsp;Luigi Cavallo and Sahika Inal*,&nbsp;","doi":"10.1021/acscentsci.4c0065410.1021/acscentsci.4c00654","DOIUrl":"https://doi.org/10.1021/acscentsci.4c00654https://doi.org/10.1021/acscentsci.4c00654","url":null,"abstract":"<p >Electron transporting (n-type) polymeric mixed conductors are an exciting class of materials for devices with aqueous electrolyte interfaces, such as bioelectronic sensors, actuators, and soft charge storage systems. However, their charge transport performance falls short of their p-type counterparts, primarily due to electrochemical side reactions such as the oxygen reduction reaction (ORR). To mitigate ORR, a common strategy in n-type organic semiconductor design focuses on lowering the lowest unoccupied molecular orbital (LUMO) level. Despite empirical observations suggesting a correlation between deep LUMO levels, low ORR, and enhanced electrochemical cycling stability in water, this relationship lacks robust evidence. In this work, we delve into the electrochemical reactions of n-type polymeric mixed conductors with varying LUMO levels and assess the impact of ORR on charge storage performance and organic electrochemical transistor (OECT) operation. Our results reveal a limited correlation between LUMO levels and ORR currents, as well as the electrochemical operational stability of the films. While ORR currents minimally contribute to OECT channel currents under fixed biasing conditions, n-type films self-discharge rapidly at floating potentials in a capacitor-like configuration. The density functional theory analysis, complemented by X-ray photoelectron spectroscopy, underscores the critical role of backbone chemistry in controlling O₂-related degradation pathways and device performance losses. These findings highlight the persistent challenge posed by ORR in n-type semiconductor design and advocate for shifting the focus toward exploring chemical moieties with limited O₂ interactions to enhance operational stability and performance at n-type film/water interfaces.</p><p >The onset of oxygen reduction reaction for n-type organic mixed ionic-electronic conductors closely aligns with their reduction onset and can hardly be mitigated by frontier energy level adjustment.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2229–2241 2229–2241"},"PeriodicalIF":12.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c00654","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143127451","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}

{"title":"Understanding Oxygen-Induced Reactions and Their Impact on n-Type Polymeric Mixed Conductor-Based Devices.","authors":"Prem D Nayak, Büsra Dereli, David Ohayon, Shofarul Wustoni, Tania Cecilia Hidalgo Castillo, Victor Druet, Yazhou Wang, Adel Hama, Craig Combe, Sophie Griggs, Maryam Alsufyani, Rajendar Sheelamanthula, Iain McCulloch, Luigi Cavallo, Sahika Inal","doi":"10.1021/acscentsci.4c00654","DOIUrl":"10.1021/acscentsci.4c00654","url":null,"abstract":"<p><p>Electron transporting (n-type) polymeric mixed conductors are an exciting class of materials for devices with aqueous electrolyte interfaces, such as bioelectronic sensors, actuators, and soft charge storage systems. However, their charge transport performance falls short of their p-type counterparts, primarily due to electrochemical side reactions such as the oxygen reduction reaction (ORR). To mitigate ORR, a common strategy in n-type organic semiconductor design focuses on lowering the lowest unoccupied molecular orbital (LUMO) level. Despite empirical observations suggesting a correlation between deep LUMO levels, low ORR, and enhanced electrochemical cycling stability in water, this relationship lacks robust evidence. In this work, we delve into the electrochemical reactions of n-type polymeric mixed conductors with varying LUMO levels and assess the impact of ORR on charge storage performance and organic electrochemical transistor (OECT) operation. Our results reveal a limited correlation between LUMO levels and ORR currents, as well as the electrochemical operational stability of the films. While ORR currents minimally contribute to OECT channel currents under fixed biasing conditions, n-type films self-discharge rapidly at floating potentials in a capacitor-like configuration. The density functional theory analysis, complemented by X-ray photoelectron spectroscopy, underscores the critical role of backbone chemistry in controlling O₂-related degradation pathways and device performance losses. These findings highlight the persistent challenge posed by ORR in n-type semiconductor design and advocate for shifting the focus toward exploring chemical moieties with limited O₂ interactions to enhance operational stability and performance at n-type film/water interfaces.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2229-2241"},"PeriodicalIF":12.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902423","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}

{"title":"Molecularly Designed and Nanoconfined Polymer Electronic Materials for Skin-like Electronics.","authors":"Yu-Qing Zheng, Zhenan Bao","doi":"10.1021/acscentsci.4c01541","DOIUrl":"10.1021/acscentsci.4c01541","url":null,"abstract":"<p><p>Stretchable electronics have seen substantial development in skin-like mechanical properties and functionality thanks to the advancements made in intrinsically stretchable polymer electronic materials. Nanoscale phase separation of polymer materials within an elastic matrix to form one-dimensional nanostructures, namely nanoconfinement, effectively reduces conformational disorders that have long impeded charge transport properties of conjugated polymers. Nanoconfinement results in enhanced charge transport and the addition of skin-like properties. In this Outlook, we highlight the current understanding of structure-property relationships for intrinsically stretchable electronic materials with a focus on the nanoconfinement strategy as a promising approach to incorporate skin-like properties and other functionalities without compromising charge transport. We outline emerging directions and challenges for intrinsically stretchable electronic materials with the aim of constructing skin-like electronic systems.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2188-2199"},"PeriodicalIF":12.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902404","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}

{"title":"Molecularly Designed and Nanoconfined Polymer Electronic Materials for Skin-like Electronics","authors":"Yu-Qing Zheng*,&nbsp; and ,&nbsp;Zhenan Bao*,&nbsp;","doi":"10.1021/acscentsci.4c0154110.1021/acscentsci.4c01541","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01541https://doi.org/10.1021/acscentsci.4c01541","url":null,"abstract":"<p >Stretchable electronics have seen substantial development in skin-like mechanical properties and functionality thanks to the advancements made in intrinsically stretchable polymer electronic materials. Nanoscale phase separation of polymer materials within an elastic matrix to form one-dimensional nanostructures, namely nanoconfinement, effectively reduces conformational disorders that have long impeded charge transport properties of conjugated polymers. Nanoconfinement results in enhanced charge transport and the addition of skin-like properties. In this Outlook, we highlight the current understanding of structure–property relationships for intrinsically stretchable electronic materials with a focus on the nanoconfinement strategy as a promising approach to incorporate skin-like properties and other functionalities without compromising charge transport. We outline emerging directions and challenges for intrinsically stretchable electronic materials with the aim of constructing skin-like electronic systems.</p><p >Nanoconfinement reduces conformational disorder in functional polymers, enhancing charge transport and enabling multiple skin-like properties through a tailored elastic matrix.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"10 12","pages":"2188–2199 2188–2199"},"PeriodicalIF":12.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143127602","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}