Jingsong Xu, Li Cao, Shuang Yang, Ying Jian, Yu Liu, Zhen Shen, Qian Liu, Xiang Chen, Min Li, Shun Li, Xiaolei Zuo, Min Li, Hua Wang
Colorectal cancer (CRC) is one of the most prevalent forms of cancer. CircRNAs have emerged as promising biomarkers for cancer diagnosis and prognosis evaluation. However, novel circRNAs as potential biomarkers for CRC still need further exploration and validation, and precise detection methods are yet to be developed. Herein, we report for the first time the use of droplets Cas13a to detect the circWDR37 as a biomarker of CRC. The arraystar circRNA microarray assays, functional experiments in vitro and in vivo, and qPCR were performed to discover and validate that circWDR37 is a biomarker for early screening and prognosis evaluation of CRC. A new technology named µDCR, which accurately detects circWDR37, has been developed by combining microfluidic droplets with CRISPR/Cas13a and recombinase polymerase amplification (RPA). Meanwhile, the role of crowding agent in improving the performance of Cas13a was uncovered. The 4% polyethylene glycol 8000 and 3% dextran‐10 significantly improved the response speed and sensitivity of one‐pot Cas13a‐RPA reaction. The detection limit of circWDR37 by µDCR was found to be 10 copies/mL, which is higher than that of qPCR. The clinical sample findings demonstrated that circWDR37 detection can be utilized to effectively screen for CRC at an early stage and enable accurate assessment of prognosis. CircWDR37 is confirmed as a groundbreaking biomarker for both diagnosis and prognosis evaluation in CRC patients. Furthermore, our innovative µDCR method for detecting circWDR37 demonstrates impressive attributes such as streamlined operation, rapidity, and high‐throughput, making it an optimal technology platform for the noninvasive screening of CRC.
{"title":"Droplets Cas13a‐RPA measurement delineates potential role for plasma circWDR37 in colorectal cancer","authors":"Jingsong Xu, Li Cao, Shuang Yang, Ying Jian, Yu Liu, Zhen Shen, Qian Liu, Xiang Chen, Min Li, Shun Li, Xiaolei Zuo, Min Li, Hua Wang","doi":"10.1002/agt2.663","DOIUrl":"https://doi.org/10.1002/agt2.663","url":null,"abstract":"Colorectal cancer (CRC) is one of the most prevalent forms of cancer. CircRNAs have emerged as promising biomarkers for cancer diagnosis and prognosis evaluation. However, novel circRNAs as potential biomarkers for CRC still need further exploration and validation, and precise detection methods are yet to be developed. Herein, we report for the first time the use of droplets Cas13a to detect the circWDR37 as a biomarker of CRC. The arraystar circRNA microarray assays, functional experiments in vitro and in vivo, and qPCR were performed to discover and validate that circWDR37 is a biomarker for early screening and prognosis evaluation of CRC. A new technology named µDCR, which accurately detects circWDR37, has been developed by combining microfluidic droplets with CRISPR/Cas13a and recombinase polymerase amplification (RPA). Meanwhile, the role of crowding agent in improving the performance of Cas13a was uncovered. The 4% polyethylene glycol 8000 and 3% dextran‐10 significantly improved the response speed and sensitivity of one‐pot Cas13a‐RPA reaction. The detection limit of circWDR37 by µDCR was found to be 10 copies/mL, which is higher than that of qPCR. The clinical sample findings demonstrated that circWDR37 detection can be utilized to effectively screen for CRC at an early stage and enable accurate assessment of prognosis. CircWDR37 is confirmed as a groundbreaking biomarker for both diagnosis and prognosis evaluation in CRC patients. Furthermore, our innovative µDCR method for detecting circWDR37 demonstrates impressive attributes such as streamlined operation, rapidity, and high‐throughput, making it an optimal technology platform for the noninvasive screening of CRC.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super‐resolution is highly demanded yet quite challenging. Herein, a ratiometric HClO probe AHOH is designed and synthesized which is capable of simultaneously staining lysosomes and mitochondria with red and green colour, respectively. AHOH could be selectivity oxidized by HClO, leading to a large emission blue shift (90 nm) and an over 1300‐fold enhancement of the emission ratio of Fl547nm/Fl637nm. We apply AHOH in super‐resolution microscopy and clearly visualize the dynamics of mitochondria–lysosomes interactions and the oxidative stress states upon different stimuli. Mitochondria dysfunction triggered by different drugs and genetic defect lead to elevated oxidative stress and higher levels of mitophagy. Moreover, AHOH could serve as a reliable tool for evaluating the efficacy of drugs regulating mitochondria dysfunction. This work provides a powerful dual‐colour super‐resolution imaging agent for real‐time monitoring the dynamics of organelle interactions and oxidative stress.
{"title":"Aggregation‐based dual‐target probe for dual‐colour super‐resolution monitoring mitophagy and evaluating drugs regulating mitochondria","authors":"Xiu‐Zhi Yang, Hongbao Fang, Shumeng Li, Chengyan Chu, Yunhua Zhang, Ying Yang, Weijiang He, Yuncong Chen, Zijian Guo","doi":"10.1002/agt2.641","DOIUrl":"https://doi.org/10.1002/agt2.641","url":null,"abstract":"Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super‐resolution is highly demanded yet quite challenging. Herein, a ratiometric HClO probe AHOH is designed and synthesized which is capable of simultaneously staining lysosomes and mitochondria with red and green colour, respectively. AHOH could be selectivity oxidized by HClO, leading to a large emission blue shift (90 nm) and an over 1300‐fold enhancement of the emission ratio of <jats:italic>Fl</jats:italic><jats:sub>547nm</jats:sub>/<jats:italic>Fl</jats:italic><jats:sub>637nm</jats:sub>. We apply AHOH in super‐resolution microscopy and clearly visualize the dynamics of mitochondria–lysosomes interactions and the oxidative stress states upon different stimuli. Mitochondria dysfunction triggered by different drugs and genetic defect lead to elevated oxidative stress and higher levels of mitophagy. Moreover, AHOH could serve as a reliable tool for evaluating the efficacy of drugs regulating mitochondria dysfunction. This work provides a powerful dual‐colour super‐resolution imaging agent for real‐time monitoring the dynamics of organelle interactions and oxidative stress.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aihui Wang, Liqun Li, Liqian Zheng, Bang‐Ping Jiang, Yihao Liu, Rimei Huang, Huimin Qiu, Shichen Ji, Hong Liang, Xing‐Can Shen
Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme‐nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme‐based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three‐dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near‐infrared light‐mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug‐resistant bacteria by the skeleton modification with genipin to produce genipin‐conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO4‐crosslinked GLZF hydrogel is constructed to sensitize the cGAS‐STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti‐recurrence of diabetic wound infection via photo‐enhanced bacterial killing and the cGAS‐STING pathway. Thereby, it paves the way to employ the universal divalent anion‐mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.
{"title":"A universal gelation strategy of bivalent anions to construct nanofibrous lysozyme hydrogels for immunomemory anti‐recurrence of diabetic wound infection by activating the cGAS‐STING pathway","authors":"Aihui Wang, Liqun Li, Liqian Zheng, Bang‐Ping Jiang, Yihao Liu, Rimei Huang, Huimin Qiu, Shichen Ji, Hong Liang, Xing‐Can Shen","doi":"10.1002/agt2.662","DOIUrl":"https://doi.org/10.1002/agt2.662","url":null,"abstract":"Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme‐nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme‐based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three‐dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near‐infrared light‐mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug‐resistant bacteria by the skeleton modification with genipin to produce genipin‐conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO<jats:sub>4</jats:sub>‐crosslinked GLZF hydrogel is constructed to sensitize the cGAS‐STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti‐recurrence of diabetic wound infection via photo‐enhanced bacterial killing and the cGAS‐STING pathway. Thereby, it paves the way to employ the universal divalent anion‐mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yansong Ren, Alexander Kravberg, Sheng Xie, Erik Svensson Grape, Zhen Yang, A. Ken Inge, Mingdi Yan, Olof Ramström
A family of responsive enaminitrile molecular switches showing tunable turn‐on fluorescence upon switching and aggregation is reported. When activated by the addition of acid/base, isomerization around the C═C bond could be effectuated, resulting in complete and reversible switching to the E‐ or Z‐isomers. Typical aggregation‐induced emission (AIE) could be recorded for one specific state of the different switches. By subtle tailoring of the parent structure, a series of compounds with emissions covering almost the full visible color range were obtained. The switchable AIE features of the enaminitrile structures enabled their demonstration as solid‐state chemosensors to detect acidic and basic vapors, where the emission displayed an “off‐on‐off” effect. Furthermore, switching to the Z‐configuration could be driven out‐of‐equilibrium through transient changes in acidity while giving rise to fluorescence. Single‐crystal X‐ray diffraction measurements suggested a luminescence mechanism based on restriction of intramolecular rotation and an intramolecular charge transfer effect in the AIE luminogens.
报告中介绍了一系列反应灵敏的烯腈分子开关，它们在切换和聚合时可发出可调的开启荧光。当加入酸/碱激活时，C═C 键周围的异构化就会发生，从而完全可逆地切换到 E 或 Z 异构体。典型的聚集诱导发射（AIE）可记录不同开关的特定状态。通过对母体结构的微妙调整，一系列化合物的发射几乎覆盖了整个可见光颜色范围。烯丙基腈结构的可切换 AIE 特性使其能够作为固态化学传感器来检测酸性和碱性蒸汽，其发射显示出 "关-开-关 "的效果。此外，在产生荧光的同时，还可以通过酸度的瞬时变化使 Z 构型的切换失去平衡。单晶 X 射线衍射测量结果表明，AIE 发光体的发光机制是基于分子内旋转限制和分子内电荷转移效应。
{"title":"Stimuli‐responsive enaminitrile molecular switches as tunable AIEgens covering the chromaticity space, operating out‐of‐equilibrium, and acting as vapor sensors","authors":"Yansong Ren, Alexander Kravberg, Sheng Xie, Erik Svensson Grape, Zhen Yang, A. Ken Inge, Mingdi Yan, Olof Ramström","doi":"10.1002/agt2.659","DOIUrl":"https://doi.org/10.1002/agt2.659","url":null,"abstract":"A family of responsive enaminitrile molecular switches showing tunable turn‐on fluorescence upon switching and aggregation is reported. When activated by the addition of acid/base, isomerization around the C═C bond could be effectuated, resulting in complete and reversible switching to the <jats:italic>E</jats:italic>‐ or <jats:italic>Z</jats:italic>‐isomers. Typical aggregation‐induced emission (AIE) could be recorded for one specific state of the different switches. By subtle tailoring of the parent structure, a series of compounds with emissions covering almost the full visible color range were obtained. The switchable AIE features of the enaminitrile structures enabled their demonstration as solid‐state chemosensors to detect acidic and basic vapors, where the emission displayed an “off‐on‐off” effect. Furthermore, switching to the <jats:italic>Z</jats:italic>‐configuration could be driven out‐of‐equilibrium through transient changes in acidity while giving rise to fluorescence. Single‐crystal X‐ray diffraction measurements suggested a luminescence mechanism based on restriction of intramolecular rotation and an intramolecular charge transfer effect in the AIE luminogens.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nematic liquid crystals (NLCs), that is, fluids with optical anisotropy as well as electric‐ and magnetic‐field responsiveness, have been widely used in commercial liquid crystal displays. Recent advancements have extended the scope of NLC molecules to large calamitic π‐conjugated systems, which heralds prospects for novel applications that exploit their superior electronic or optical functionalities in, for example, electric field controlled fluorescence switch devices. However, NLC phases of such extended π‐systems usually flow only at high temperatures, which hampers device applications that operate around room temperature. Here, we show near‐room‐temperature NLCs of a π‐conjugated fluorophore by introducing a flexible cyclic structure into the mesogenic core. 3,8‐Bis(4‐propylphenyl)‐6,7‐dihydro‐5H‐benzo[7]annulene (DPB[7]‐C3) has a nematic phase in a significantly lower temperature range (52.6–160.4°C) than the DPB[7]‐C3 analog without flexible alkylene bridges, (E)‐4‐propyl‐4′‐(4‐propylstyryl)‐1,1′‐biphenyl (248–262°C). We attribute this large decrease in the phase transition temperature to large intramolecular conformational entropies that arise from the geometric change of the cyclic structure, which involves rotational motion of single biaryl‐bonds and bending motions along the long molecular axis in the thermal equilibrium state. The practical utility of these NLC molecules is demonstrated by preparing an electric‐field‐responsive large‐area fluorescent switch device with a sub‐millisecond response time from a mixture of 3,8‐bis(4‐alkylphenyl)‐6,7‐dihydro‐5H‐benzo[7]annulenes (DPB[7]‐Cns).
{"title":"Near‐room‐temperature π‐conjugated nematic liquid crystals in molecules with a flexible seven‐membered ring structure","authors":"Riki Iwai, Hiroyuki Yoshida, Yuki Arakawa, Shunsuke Sasaki, Yuuto Iida, Kazunobu Igawa, Tsuneaki Sakurai, Satoshi Suzuki, Masatoshi Tokita, Junji Watanabe, Gen‐ichi Konishi","doi":"10.1002/agt2.660","DOIUrl":"https://doi.org/10.1002/agt2.660","url":null,"abstract":"Nematic liquid crystals (NLCs), that is, fluids with optical anisotropy as well as electric‐ and magnetic‐field responsiveness, have been widely used in commercial liquid crystal displays. Recent advancements have extended the scope of NLC molecules to large calamitic π‐conjugated systems, which heralds prospects for novel applications that exploit their superior electronic or optical functionalities in, for example, electric field controlled fluorescence switch devices. However, NLC phases of such extended π‐systems usually flow only at high temperatures, which hampers device applications that operate around room temperature. Here, we show near‐room‐temperature NLCs of a π‐conjugated fluorophore by introducing a flexible cyclic structure into the mesogenic core. 3,8‐Bis(4‐propylphenyl)‐6,7‐dihydro‐5<jats:italic>H</jats:italic>‐benzo[7]annulene (DPB[7]‐C3) has a nematic phase in a significantly lower temperature range (52.6–160.4°C) than the DPB[7]‐C3 analog without flexible alkylene bridges, (<jats:italic>E</jats:italic>)‐4‐propyl‐4′‐(4‐propylstyryl)‐1,1′‐biphenyl (248–262°C). We attribute this large decrease in the phase transition temperature to large intramolecular conformational entropies that arise from the geometric change of the cyclic structure, which involves rotational motion of single biaryl‐bonds and bending motions along the long molecular axis in the thermal equilibrium state. The practical utility of these NLC molecules is demonstrated by preparing an electric‐field‐responsive large‐area fluorescent switch device with a sub‐millisecond response time from a mixture of 3,8‐bis(4‐alkylphenyl)‐6,7‐dihydro‐5<jats:italic>H</jats:italic>‐benzo[7]annulenes (DPB[7]‐C<jats:italic>n</jats:italic>s).","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhenxin Yang, Jiale Su, Junzhan Wang, Xuanhe Li, Fushun Li, Juntao Hu, Nan Chen, Zhang Tao, Delong Yang, Deng‐Ke Wang, Qiang Zhu, Yuhui Liao, Zheng‐Hong Lu
Solution coating of organic semiconductors offers great potential for achieving low‐cost and high‐throughput manufacturing of large‐area and flexible electronics. However, the solution processability of semiconducting small molecules for fabricating uniform and reliable thin‐film devices poses challenges due to the low viscosities of small‐molecule solutions. Here, we report a universal approach employing a primer template (PT) to enhance the spreadability of small‐molecule solutions on silicon wafers, enabling the spin‐coating fabrication of uniform thin films composed of millimeter‐scale grains with complete large‐area coverage and well‐ordered molecular packing. Using PT, we fabricated organic thin‐film transistors (OTFTs) using solutions containing various small molecules such as rubrene and 2‐decyl‐7‐phenyl‐[1]benzothieno[3,2‐b][1]benzothiophene. The device yield of all fabricated OTFTs is consistently 100% while achieving a high average mobility of 1.62 cm2 V−1 s−1 with a device‐to‐device variation of 7.7% measured in ambient air condition. In addition, the utilization of PT resulted in a batch‐to‐batch variation of 12.5% in device performance over dozens of OTFT devices. The key industrial manufacturing metrics, such as device yield, reproducibility, and performance uniformity of the PT OTFTs, are among the best for devices fabricated using solution spin‐coating techniques.
{"title":"Spin‐coating fabrication of high‐yield and uniform organic thin‐film transistors via a primer template growth","authors":"Zhenxin Yang, Jiale Su, Junzhan Wang, Xuanhe Li, Fushun Li, Juntao Hu, Nan Chen, Zhang Tao, Delong Yang, Deng‐Ke Wang, Qiang Zhu, Yuhui Liao, Zheng‐Hong Lu","doi":"10.1002/agt2.661","DOIUrl":"https://doi.org/10.1002/agt2.661","url":null,"abstract":"Solution coating of organic semiconductors offers great potential for achieving low‐cost and high‐throughput manufacturing of large‐area and flexible electronics. However, the solution processability of semiconducting small molecules for fabricating uniform and reliable thin‐film devices poses challenges due to the low viscosities of small‐molecule solutions. Here, we report a universal approach employing a primer template (PT) to enhance the spreadability of small‐molecule solutions on silicon wafers, enabling the spin‐coating fabrication of uniform thin films composed of millimeter‐scale grains with complete large‐area coverage and well‐ordered molecular packing. Using PT, we fabricated organic thin‐film transistors (OTFTs) using solutions containing various small molecules such as rubrene and 2‐decyl‐7‐phenyl‐[1]benzothieno[3,2‐b][1]benzothiophene. The device yield of all fabricated OTFTs is consistently 100% while achieving a high average mobility of 1.62 cm<jats:sup>2</jats:sup> V<jats:sup>−1</jats:sup> s<jats:sup>−1</jats:sup> with a device‐to‐device variation of 7.7% measured in ambient air condition. In addition, the utilization of PT resulted in a batch‐to‐batch variation of 12.5% in device performance over dozens of OTFT devices. The key industrial manufacturing metrics, such as device yield, reproducibility, and performance uniformity of the PT OTFTs, are among the best for devices fabricated using solution spin‐coating techniques.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phototheranostics has garnered sustained attention due to its significant potential for revolutionizing conventional cancer treatment strategies. While being one of the most commonly employed strategies for constructing phototheranostic systems by engineering the integration of photosensitizers (PSs) into nanosystems, nano‐PSs face challenges including complexity in the preparation process, low delivery efficiency, and potential toxicity issues. Contrastingly, the burgeoning popularity of small molecule PSs characterized by aggregation‐induced emission (AIE) has become evident in the arena of cancer phototheranostics. This preference is underscored by their well‐defined structures, adjustable photophysical properties, and low toxicity. Therefore, acquiring profound insights into the pioneering strides achievable through a solitary small molecule PS with AIE in tumor phototheranostics is of paramount scientific significance. In this review, we will discuss the recent progress of small molecule PSs with AIE properties in cancer diagnosis and phototherapies with representative examples, guided by the ethos of “Complexity made easy”. We also look forward to the future development direction of AIE small molecules, with a central objective of advancing cancer research through a focal emphasis on simplicity, expeditiousness, and safety.
{"title":"Complexity made easy: Aggregation‐induced emission small molecules for cancer diagnosis and phototherapies","authors":"Luojia Chen, Si‐Ling Chen, Yuncong Yuan, Xiang Leng, Xiaoyu Xu, Jingyuan Chen, Jiayi Shi, Kun Qian, Yuanlong Xie, Qihang Ding, Zhen Cheng, Meijia Gu","doi":"10.1002/agt2.657","DOIUrl":"https://doi.org/10.1002/agt2.657","url":null,"abstract":"Phototheranostics has garnered sustained attention due to its significant potential for revolutionizing conventional cancer treatment strategies. While being one of the most commonly employed strategies for constructing phototheranostic systems by engineering the integration of photosensitizers (PSs) into nanosystems, nano‐PSs face challenges including complexity in the preparation process, low delivery efficiency, and potential toxicity issues. Contrastingly, the burgeoning popularity of small molecule PSs characterized by aggregation‐induced emission (AIE) has become evident in the arena of cancer phototheranostics. This preference is underscored by their well‐defined structures, adjustable photophysical properties, and low toxicity. Therefore, acquiring profound insights into the pioneering strides achievable through a solitary small molecule PS with AIE in tumor phototheranostics is of paramount scientific significance. In this review, we will discuss the recent progress of small molecule PSs with AIE properties in cancer diagnosis and phototherapies with representative examples, guided by the ethos of “Complexity made easy”. We also look forward to the future development direction of AIE small molecules, with a central objective of advancing cancer research through a focal emphasis on simplicity, expeditiousness, and safety.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteosarcoma (OS) is characterized by an unfavorable prognosis and high mortality rates, with the local recurrence attributed to residual lesions post‐surgery being a major reason for treatment failure. Precise and tumor‐specific resection guidance to minimize recurrence remains a significant challenge. In the present study, a nanosystem based on aggregation‐induced emission (AIE) molecules with emission in the second near‐infrared window is proposed for the synergistic fluorescence (FL) and chemiluminescence (CL) imaging‐guided surgical resection for the elimination of tumor foci. The designed AIE molecule, BBTD14, exhibits stable FL with a high quantum yield of up to 3.95%, which effectively matches the energy levels of CL high‐energy states, generating the longest emission wavelength of CL reported to date. Targeted tumor imaging‐guided surgery (IGS) is facilitated by FL and CL nanoprobes (FLNP and CLNP) constructed based on BBTD14. During OS surgery, the FLNP, with the stability of FL and a high targeting capability, was first intravenously used to guide the surgical removal of the main tumor. Subsequently, CLNP was locally incubated to facilitate rapid and accurate evaluation of residual tumors at the operative border. High signal‐to‐noise ratio CL imaging was achieved after spraying with hydrogen peroxide, thereby overcoming the limitations of intraoperative frozen sections. The proposed technique also significantly reduced the recurrence rates in OS mouse models and exhibited high marker specificity in ex vivo OS patient pathology samples, confirming its potential in clinical applications and providing a unique perspective for developing IGS.
{"title":"NIR‐II AIEgens nanosystem for fluorescence and chemiluminescence synergistic imaging‐guided precise resection in osteosarcoma surgery","authors":"Ruotong Li, Kaiyuan Liu, Qian Hu, Jiakang Shen, Dongqing Zuo, Hongsheng Wang, Xingjun Zhu, Wei Sun","doi":"10.1002/agt2.658","DOIUrl":"https://doi.org/10.1002/agt2.658","url":null,"abstract":"Osteosarcoma (OS) is characterized by an unfavorable prognosis and high mortality rates, with the local recurrence attributed to residual lesions post‐surgery being a major reason for treatment failure. Precise and tumor‐specific resection guidance to minimize recurrence remains a significant challenge. In the present study, a nanosystem based on aggregation‐induced emission (AIE) molecules with emission in the second near‐infrared window is proposed for the synergistic fluorescence (FL) and chemiluminescence (CL) imaging‐guided surgical resection for the elimination of tumor foci. The designed AIE molecule, BBTD14, exhibits stable FL with a high quantum yield of up to 3.95%, which effectively matches the energy levels of CL high‐energy states, generating the longest emission wavelength of CL reported to date. Targeted tumor imaging‐guided surgery (IGS) is facilitated by FL and CL nanoprobes (FLNP and CLNP) constructed based on BBTD14. During OS surgery, the FLNP, with the stability of FL and a high targeting capability, was first intravenously used to guide the surgical removal of the main tumor. Subsequently, CLNP was locally incubated to facilitate rapid and accurate evaluation of residual tumors at the operative border. High signal‐to‐noise ratio CL imaging was achieved after spraying with hydrogen peroxide, thereby overcoming the limitations of intraoperative frozen sections. The proposed technique also significantly reduced the recurrence rates in OS mouse models and exhibited high marker specificity in <jats:italic>ex vivo</jats:italic> OS patient pathology samples, confirming its potential in clinical applications and providing a unique perspective for developing IGS.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Javad Tavakoli, Qi Hu, Joanne L. Tipper, Youhong Tang
In recent years, the substantial increase in total joint replacements for treating degenerative joint disease has heightened concerns regarding implant loosening and failure. This is especially critical as more young patients are undergoing both initial and subsequent joint replacement procedures. These complications often necessitate additional revision surgeries. Unfortunately, current clinical practices lack effective methods for the early detection of implant failure, and there is a noticeable absence of strategies utilizing molecular markers to identify post‐surgery implant issues. This article critically assesses the potential of aggregation‐induced emission (AIE) biomarkers in detecting molecular markers relevant to implant failure. It begins by outlining the pathogenesis of implant loosening and identifying pertinent molecular markers. The study then delves into how AIE luminogens (AIEgens) can play a crucial role in detecting processes such as osteogenesis and osteoclastogenesis. Notably, it discusses the utilization of AIEgens in detecting key molecular markers, including TNF‐α, osteocalcin, and urinary N‐terminal telopeptide. The prospect of AIE biomarkers for the early detection of bone loss and implant failure presents a promising avenue for enhancing our understanding of skeletal health and improving clinical outcomes through timely intervention and personalized treatment approaches. Ongoing research and development in this area are crucial for translating AIE‐based technologies into practical tools for optimizing bone health management.
{"title":"Aggregation‐induced emission biomarkers for early detection of orthopaedic implant failure","authors":"Javad Tavakoli, Qi Hu, Joanne L. Tipper, Youhong Tang","doi":"10.1002/agt2.645","DOIUrl":"https://doi.org/10.1002/agt2.645","url":null,"abstract":"In recent years, the substantial increase in total joint replacements for treating degenerative joint disease has heightened concerns regarding implant loosening and failure. This is especially critical as more young patients are undergoing both initial and subsequent joint replacement procedures. These complications often necessitate additional revision surgeries. Unfortunately, current clinical practices lack effective methods for the early detection of implant failure, and there is a noticeable absence of strategies utilizing molecular markers to identify post‐surgery implant issues. This article critically assesses the potential of aggregation‐induced emission (AIE) biomarkers in detecting molecular markers relevant to implant failure. It begins by outlining the pathogenesis of implant loosening and identifying pertinent molecular markers. The study then delves into how AIE luminogens (AIEgens) can play a crucial role in detecting processes such as osteogenesis and osteoclastogenesis. Notably, it discusses the utilization of AIEgens in detecting key molecular markers, including TNF‐α, osteocalcin, and urinary N‐terminal telopeptide. The prospect of AIE biomarkers for the early detection of bone loss and implant failure presents a promising avenue for enhancing our understanding of skeletal health and improving clinical outcomes through timely intervention and personalized treatment approaches. Ongoing research and development in this area are crucial for translating AIE‐based technologies into practical tools for optimizing bone health management.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The elucidation of hierarchical assembly structure of metal nanoclusters is of fundamental importance in the context of bottom‐up fabrication and functionalization. While recent studies have provided valuable insights into the multiscale assembly patterns of gold or silver‐based nanoclusters, the success in achieving similar results for copper analogues has been notably limited. Herein, by virtue of a slow‐ligand‐release strategy, a copper nanocluster denoted as [Cu66Cl8(PPh3)8(SC2H5)32H24](SbF6)2 was synthesized, resulting in the formation of fresh hierarchical assembly structures in one‐pot. The arrangement of the metal atoms within the cluster reveals an orderly of 16 Cu4 squares, representing a rare copper nanocluster comprising square motifs. Additionally, the ligands (phosphine, thiolate, and halide) coordinate to the surface of the cluster in a regiospecific manner, displaying square patterns as well. The self‐assembly facilitated by the C‐H···F interaction between the cluster moieties and SbF6− anions further induces the formation of three‐dimensional cubes and eventually large nanocrystals. Density functional theoretical (DFT) calculations reveal that hydride atoms with low chemical shifts typically exhibit short Cu‐H distances. The cluster demonstrates moderate stability and high catalytic activity in the chemoselective hydrogenation of cyclohexanone under mild conditions.
{"title":"Cu66 nanoclusters from hierarchical square motifs: Synthesis, assembly, and catalysis","authors":"Xueli Sun, Yuchen Wang, Qingyuan Wu, Ying‐Zi Han, Xuekun Gong, Xiongkai Tang, Christine M. Aikens, Hui Shen, Nanfeng Zheng","doi":"10.1002/agt2.651","DOIUrl":"https://doi.org/10.1002/agt2.651","url":null,"abstract":"The elucidation of hierarchical assembly structure of metal nanoclusters is of fundamental importance in the context of bottom‐up fabrication and functionalization. While recent studies have provided valuable insights into the multiscale assembly patterns of gold or silver‐based nanoclusters, the success in achieving similar results for copper analogues has been notably limited. Herein, by virtue of a slow‐ligand‐release strategy, a copper nanocluster denoted as [Cu<jats:sub>66</jats:sub>Cl<jats:sub>8</jats:sub>(PPh<jats:sub>3</jats:sub>)<jats:sub>8</jats:sub>(SC<jats:sub>2</jats:sub>H<jats:sub>5</jats:sub>)<jats:sub>32</jats:sub>H<jats:sub>24</jats:sub>](SbF<jats:sub>6</jats:sub>)<jats:sub>2</jats:sub> was synthesized, resulting in the formation of fresh hierarchical assembly structures in one‐pot. The arrangement of the metal atoms within the cluster reveals an orderly of 16 Cu<jats:sub>4</jats:sub> squares, representing a rare copper nanocluster comprising square motifs. Additionally, the ligands (phosphine, thiolate, and halide) coordinate to the surface of the cluster in a regiospecific manner, displaying square patterns as well. The self‐assembly facilitated by the C‐H···F interaction between the cluster moieties and SbF<jats:sub>6</jats:sub><jats:sup>−</jats:sup> anions further induces the formation of three‐dimensional cubes and eventually large nanocrystals. Density functional theoretical (DFT) calculations reveal that hydride atoms with low chemical shifts typically exhibit short Cu‐H distances. The cluster demonstrates moderate stability and high catalytic activity in the chemoselective hydrogenation of cyclohexanone under mild conditions.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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