Nicholas D. Calvert, Luciana Yu, Olivia C. Sehl, Julia J. Gevaert, Natasha N. Knier, Angelie Rivera‐Rodriguez, Clara S. Goulet, Nitara Fernando, Samantha Flood, Carlos M. Rinaldi‐Ramos, Paula J. Foster, Adam J. Shuhendler
The increased clinical application of cell‐based therapies has resulted in a parallel increase in the need for non‐invasive imaging‐based approaches for cell tracking, often through labeling with nanoparticles. An ideal nanoparticle for such applications must be biologically compatible as well as readily internalized by cells to ensure adequate and stable cell loading. Surface coatings have been used to make nanoparticle trackers suitable for these purposes, but those currently employed tend to have cytotoxic effects. Zwitterionic ligands are known to be biocompatible and antifouling; however, head‐to‐head evaluation of specific zwitterionic ligands for cell loading has not yet been explored. Magnetic particle imaging (MPI) detects superparamagnetic iron oxide nanoparticles (SPIONs) using time‐varying magnetic fields. Because MPI can produce high‐contrast, real‐time images with no tissue depth limitation, it is an ideal candidate for in vivo cell tracking. In this work, we have conjugated hard (permanently charged) and soft (pKa‐dependently charged) biomimetic zwitterionic ligands to SPIONs and characterized how these ligands changed SPION physicochemical properties. We have evaluated cellular uptake and subcellular localization between zwitterions, how the improvement in cell uptake generated stronger MPI signal for smaller numbers of cells, and how these cells can be tracked in an animal model with greater sensitivity for longer periods of time. Our best‐performing surface coating afforded high cell loading within 4 h, with full signal retention in vivo over 7 days.
{"title":"The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking","authors":"Nicholas D. Calvert, Luciana Yu, Olivia C. Sehl, Julia J. Gevaert, Natasha N. Knier, Angelie Rivera‐Rodriguez, Clara S. Goulet, Nitara Fernando, Samantha Flood, Carlos M. Rinaldi‐Ramos, Paula J. Foster, Adam J. Shuhendler","doi":"10.1002/agt2.609","DOIUrl":"https://doi.org/10.1002/agt2.609","url":null,"abstract":"The increased clinical application of cell‐based therapies has resulted in a parallel increase in the need for non‐invasive imaging‐based approaches for cell tracking, often through labeling with nanoparticles. An ideal nanoparticle for such applications must be biologically compatible as well as readily internalized by cells to ensure adequate and stable cell loading. Surface coatings have been used to make nanoparticle trackers suitable for these purposes, but those currently employed tend to have cytotoxic effects. Zwitterionic ligands are known to be biocompatible and antifouling; however, head‐to‐head evaluation of specific zwitterionic ligands for cell loading has not yet been explored. Magnetic particle imaging (MPI) detects superparamagnetic iron oxide nanoparticles (SPIONs) using time‐varying magnetic fields. Because MPI can produce high‐contrast, real‐time images with no tissue depth limitation, it is an ideal candidate for in vivo cell tracking. In this work, we have conjugated hard (permanently charged) and soft (pKa‐dependently charged) biomimetic zwitterionic ligands to SPIONs and characterized how these ligands changed SPION physicochemical properties. We have evaluated cellular uptake and subcellular localization between zwitterions, how the improvement in cell uptake generated stronger MPI signal for smaller numbers of cells, and how these cells can be tracked in an animal model with greater sensitivity for longer periods of time. Our best‐performing surface coating afforded high cell loading within 4 h, with full signal retention in vivo over 7 days.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567369","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}
Chemodynamic therapy (CDT) has shown promising antitumor effects in various malignant tumors. However, its application for glioblastoma (GBM) is significantly hindered by the challenge of delivering CDT agents across the blood‐brain barrier (BBB) and achieving efficient tumor targeting. To overcome these obstacles, this study presents a novel DNA nanomachine (Cu@tFNAs‐G‐A NM) by loading copper ions (Cu2+) onto tetrahedral framework nucleic acids (tFNAs) functionalized with dual DNA aptamers. The dual DNA aptamers (GS24 for BBB penetration and AS1411 for tumor targeting) empowered Cu@tFNAs‐G‐A NM with the ability to effectively penetrate the BBB and selectively accumulate in tumor cells. Upon internalization, the loaded Cu2+ reacted with tumor‐overexpressed reductive glutathione (GSH) and hydrogen peroxide (H2O2), generating hydroxyl radicals (·OH) and inducing tumor cell death. Additionally, Cu@tFNAs‐G‐A NM was found to be rapidly cleared from the brain and normal tissues within 24 h, minimizing potential systemic toxic side effects. These findings demonstrate the promising potential of Cu@tFNAs‐G‐A NM for effective CDT against GBM and open up new avenues for the development of targeted therapies for GBM.
{"title":"DNA nanomachine‐driven chemodynamic therapy against glioblastoma","authors":"Xiaodie Li, Yufei Lan, Xin Fu, Xin Luo, Jie Chen, Wenxin Zhang, Boming Zuo, Tao Yang, Boyang Liu, Chao Zhang, Hongbo Guo","doi":"10.1002/agt2.603","DOIUrl":"https://doi.org/10.1002/agt2.603","url":null,"abstract":"Chemodynamic therapy (CDT) has shown promising antitumor effects in various malignant tumors. However, its application for glioblastoma (GBM) is significantly hindered by the challenge of delivering CDT agents across the blood‐brain barrier (BBB) and achieving efficient tumor targeting. To overcome these obstacles, this study presents a novel DNA nanomachine (Cu@tFNAs‐G‐A NM) by loading copper ions (Cu<jats:sup>2+</jats:sup>) onto tetrahedral framework nucleic acids (tFNAs) functionalized with dual DNA aptamers. The dual DNA aptamers (GS24 for BBB penetration and AS1411 for tumor targeting) empowered Cu@tFNAs‐G‐A NM with the ability to effectively penetrate the BBB and selectively accumulate in tumor cells. Upon internalization, the loaded Cu<jats:sup>2+</jats:sup> reacted with tumor‐overexpressed reductive glutathione (GSH) and hydrogen peroxide (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>), generating hydroxyl radicals (·OH) and inducing tumor cell death. Additionally, Cu@tFNAs‐G‐A NM was found to be rapidly cleared from the brain and normal tissues within 24 h, minimizing potential systemic toxic side effects. These findings demonstrate the promising potential of Cu@tFNAs‐G‐A NM for effective CDT against GBM and open up new avenues for the development of targeted therapies for GBM.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567370","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}
This study presents a novel boron‐difluoride complex‐based fluorescent nanofilm sensor capable of detecting sarin vapors in the environment by reporting an output fluorescence signal. The sensor's evaluation demonstrated an exceptionally low detection limit for sarin vapor, even in the presence of various interfering gases, with theoretical and practical limits of detection of 0.7 and 1 ppb, respectively. The sensor featured a rapid response time (less than 2 s), a broad linear detection range (1 ppb–1000 ppm), and superior selectivity for sarin vapor over a group of interfering analytes, outperforming existing sarin sensors. Mechanistic study indicates that the sensor's heightened sensitivity to sarin vapor is due to the robust affinity of nitrogen atoms within the core BODIQ unit for sarin. Additionally, the tetraphenylethylene structure with steric hindrance effectively inhibits the tight packing of BODIQ derivatives, and forms numerous microporous structures in the self‐assembled nanofilm, which are beneficial for the mass transfer, enhancing the sensor efficiency in detecting vapors. Furthermore, we have achieved the differentiation of sarin, diethyl chlorophosphate, and HCl vapor through the analysis of sensing kinetic. This fluorescent sensor opens new avenues for sustainable, low‐cost, and environment‐friendly portable devices, as well as for environmental monitoring and tracking applications.
{"title":"Dynamic response and discrimination of gaseous sarin using a boron‐difluoride complex film‐based fluorescence sensor","authors":"Zhijie Zhou, Lei Zhang, Lingya Peng, Yingjie Li, Xiaolin Zhu, Yidi Wu, Zebiao Qiu, Gang He, Molin Qin, Haonan Peng, Yu Fang","doi":"10.1002/agt2.629","DOIUrl":"https://doi.org/10.1002/agt2.629","url":null,"abstract":"This study presents a novel boron‐difluoride complex‐based fluorescent nanofilm sensor capable of detecting sarin vapors in the environment by reporting an output fluorescence signal. The sensor's evaluation demonstrated an exceptionally low detection limit for sarin vapor, even in the presence of various interfering gases, with theoretical and practical limits of detection of 0.7 and 1 ppb, respectively. The sensor featured a rapid response time (less than 2 s), a broad linear detection range (1 ppb–1000 ppm), and superior selectivity for sarin vapor over a group of interfering analytes, outperforming existing sarin sensors. Mechanistic study indicates that the sensor's heightened sensitivity to sarin vapor is due to the robust affinity of nitrogen atoms within the core BODIQ unit for sarin. Additionally, the tetraphenylethylene structure with steric hindrance effectively inhibits the tight packing of BODIQ derivatives, and forms numerous microporous structures in the self‐assembled nanofilm, which are beneficial for the mass transfer, enhancing the sensor efficiency in detecting vapors. Furthermore, we have achieved the differentiation of sarin, diethyl chlorophosphate, and HCl vapor through the analysis of sensing kinetic. This fluorescent sensor opens new avenues for sustainable, low‐cost, and environment‐friendly portable devices, as well as for environmental monitoring and tracking applications.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141551785","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}
Guangtao Gao, Junyi Che, Peipei Xu, Bing Chen, Yuanjin Zhao
Several therapeutic drugs including heptamethine cyanine dye (IR‐780), doxorubicin (DOX), and others have exhibited positive outcomes in the treatment of multiple myeloma (MM). However, curing MM is still hampered by undesired off‐target effects and uncontrolled release of the therapeutics. Herein, we present novel MM‐mimicking nanocarriers by integration of DOX, IR‐780, and MM cell membrane with zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles (D/INPs@CM) for MM treatment. The nanocarriers were fabricated by co‐loading DOX and IR‐780 into ZIF‐8 and further coated with the cell membrane. After intravenous injection, the D/INPs@CM can enter the bone marrow and target the tumor cells owing to bone marrow homing and homologous targeting properties of the MM cell membrane. Once accumulating in the tumor site, ZIF‐8 decomposed under the acid microenvironment and released the encapsulated DOX and IR‐780. As a result, D/INPs@CM showed the best MM tumor eradication performance compared to D/INPs, without displaying noticeable systemic toxicity. All these features suggest that our biomimetic nanocarriers may have great potential for the precise and targeted therapy of MM and related other hematological malignancies.
包括七亚甲基青染料（IR-780）、多柔比星（DOX）等在内的多种治疗药物在治疗多发性骨髓瘤（MM）方面取得了积极成果。然而，治疗多发性骨髓瘤仍然受到非预期的脱靶效应和治疗药物不可控释放的阻碍。在此，我们通过将 DOX、IR-780 和 MM 细胞膜与沸石咪唑啉框架-8（ZIF-8）纳米颗粒（D/INPs@CM）整合在一起，提出了用于 MM 治疗的新型 MM 拟态纳米载体。这种纳米载体是将DOX和IR-780共负载到ZIF-8中并进一步包覆细胞膜而制成的。静脉注射后，D/INPs@CM可进入骨髓并靶向肿瘤细胞，这是由于骨髓归巢和MM细胞膜的同源靶向特性。在肿瘤部位聚集后，ZIF-8 在酸性微环境下分解，释放出包裹的 DOX 和 IR-780。因此，与D/INPs相比，D/INPs@CM显示出最佳的MM肿瘤根除性能，而且没有显示出明显的全身毒性。所有这些特点都表明，我们的仿生纳米载体在精确靶向治疗 MM 及其他相关血液恶性肿瘤方面具有巨大潜力。
{"title":"Biomimetic cell membrane decorated ZIF‐8 nanocarriers with IR‐780 and doxorubicin loading for multiple myeloma treatment","authors":"Guangtao Gao, Junyi Che, Peipei Xu, Bing Chen, Yuanjin Zhao","doi":"10.1002/agt2.631","DOIUrl":"https://doi.org/10.1002/agt2.631","url":null,"abstract":"Several therapeutic drugs including heptamethine cyanine dye (IR‐780), doxorubicin (DOX), and others have exhibited positive outcomes in the treatment of multiple myeloma (MM). However, curing MM is still hampered by undesired off‐target effects and uncontrolled release of the therapeutics. Herein, we present novel MM‐mimicking nanocarriers by integration of DOX, IR‐780, and MM cell membrane with zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles (D/INPs@CM) for MM treatment. The nanocarriers were fabricated by co‐loading DOX and IR‐780 into ZIF‐8 and further coated with the cell membrane. After intravenous injection, the D/INPs@CM can enter the bone marrow and target the tumor cells owing to bone marrow homing and homologous targeting properties of the MM cell membrane. Once accumulating in the tumor site, ZIF‐8 decomposed under the acid microenvironment and released the encapsulated DOX and IR‐780. As a result, D/INPs@CM showed the best MM tumor eradication performance compared to D/INPs, without displaying noticeable systemic toxicity. All these features suggest that our biomimetic nanocarriers may have great potential for the precise and targeted therapy of MM and related other hematological malignancies.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141551786","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}
Yue Zhao, Fuhao An, Jichao Wu, Haining Li, Xueyu Wang, Lanya Jiao, Ying Kong, Jinghan Zhu, Xun Sun, Xu Li, Miao Wang, Yu Zhang, Xuan Sun
Photothermal agents (PTAs) with ultra‐high photothermal conversion efficiency (PCE) activated upon near‐infrared (NIR) laser irradiation can heat up and destroy tumor cells under low‐intensity laser excitation to allow safe and efficient tumor therapy. Herein, an organic PTA with an outstanding PCE of 89.6% is developed from rationally designed perylene diimide (PDI) with electron‐donating cyclohexylamine moiety at the bay‐positions of its skeleton and chiral phenethylamine (PEA) moiety at its N terminals, termed here PEAPDI. The strong intermolecular interaction between the PDI skeletons induced by PEA together with the intramolecular charge transfer from cyclohexylamine to PDI skeleton severely quenches the fluorescence emission from PEAPDI and significantly enhances its NIR absorption, resulting in super NIR–photothermal conversion. PEAPDI molecules are subsequently encapsulated within silica nanocapsules (SNCs), creating PEAPDI@SNC. Characterized by its small hydrodynamic diameter, monodispersity, high PDI encapsulation efficiency, colloidal stability, and biocompatibility, PEAPDI@SNC exhibits prolonged blood circulation and enhanced permeability and retention effect, enabling targeted accumulation at the tumor site. An in vivo study using a 4T1 tumor–bearing mice model illustrates the agent's potent tumor ablation capability without side effects at low dosage under NIR laser irradiation (808 nm). The findings demonstrate PEAPDI@SNC's significant potential as a PTA for tumor treatment.
{"title":"Chiral‐induced highly efficient NIR–photothermal conversion of perylene diimide@silica nanocapsules for photothermal therapy","authors":"Yue Zhao, Fuhao An, Jichao Wu, Haining Li, Xueyu Wang, Lanya Jiao, Ying Kong, Jinghan Zhu, Xun Sun, Xu Li, Miao Wang, Yu Zhang, Xuan Sun","doi":"10.1002/agt2.630","DOIUrl":"https://doi.org/10.1002/agt2.630","url":null,"abstract":"Photothermal agents (PTAs) with ultra‐high photothermal conversion efficiency (PCE) activated upon near‐infrared (NIR) laser irradiation can heat up and destroy tumor cells under low‐intensity laser excitation to allow safe and efficient tumor therapy. Herein, an organic PTA with an outstanding PCE of 89.6% is developed from rationally designed perylene diimide (PDI) with electron‐donating cyclohexylamine moiety at the bay‐positions of its skeleton and chiral phenethylamine (PEA) moiety at its N terminals, termed here PEAPDI. The strong intermolecular interaction between the PDI skeletons induced by PEA together with the intramolecular charge transfer from cyclohexylamine to PDI skeleton severely quenches the fluorescence emission from PEAPDI and significantly enhances its NIR absorption, resulting in super NIR–photothermal conversion. PEAPDI molecules are subsequently encapsulated within silica nanocapsules (SNCs), creating PEAPDI@SNC. Characterized by its small hydrodynamic diameter, monodispersity, high PDI encapsulation efficiency, colloidal stability, and biocompatibility, PEAPDI@SNC exhibits prolonged blood circulation and enhanced permeability and retention effect, enabling targeted accumulation at the tumor site. An in vivo study using a 4T1 tumor–bearing mice model illustrates the agent's potent tumor ablation capability without side effects at low dosage under NIR laser irradiation (808 nm). The findings demonstrate PEAPDI@SNC's significant potential as a PTA for tumor treatment.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141513767","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}
Si Tang, Lingyu Sun, Huiyao Shi, Kaixuan Wang, Jialin Shi, Chanmin Su, Yuanjin Zhao, Lianqing Liu
Cardiac diseases threaten human health and burden the global healthcare system. Cardiomyocytes (CMs) are considered the ideal model for studying the signal transduction and regulation of cardiac systems. Based on the principle of the rhythmical beating process (excitation‒contraction coupling mechanism of CMs), investigating the mechanical and electrophysiological signals offered new hope for cardiac disease detection, prevention, and treatment. Considerable technological success has been achieved in electromechanical signal recording. However, most drug assessment platforms attach importance to high‐throughput and dynamic monitoring of mechanical or electrical signals while overlooking the measuring principles and physiological significance of the signal. In this review, the development of biosensing platforms for CMs, sensing principles, key measured parameters, measurement accuracy, and limitations are discussed. Additionally, various approaches for the stimulation and measurement of CMs in vitro are discussed to further elucidate the response of these cells to external stimuli. Furthermore, disease modeling and drug screening are used as examples to intuitively demonstrate the contribution of in vitro CM measurement platforms to the biomedical field, thereby further illustrating the challenges and prospects of these sensing platforms.
心脏疾病威胁着人类健康，并给全球医疗保健系统带来沉重负担。心肌细胞（CMs）被认为是研究心脏系统信号转导和调节的理想模型。基于节律性跳动过程（CM 的兴奋-收缩耦合机制）的原理，研究机械和电生理信号为心脏疾病的检测、预防和治疗提供了新的希望。机电信号记录技术已取得了巨大成功。然而，大多数药物评估平台重视机械或电信号的高通量和动态监测，却忽视了信号的测量原理和生理意义。本综述讨论了中药生物传感平台的发展、传感原理、关键测量参数、测量精度和局限性。此外，还讨论了体外刺激和测量 CMs 的各种方法，以进一步阐明这些细胞对外部刺激的反应。此外，还以疾病建模和药物筛选为例，直观地展示了体外 CM 测量平台对生物医学领域的贡献，从而进一步说明了这些传感平台所面临的挑战和前景。
{"title":"Emerging biotechnologies for screening electromechanical signals of cardiomyocytes","authors":"Si Tang, Lingyu Sun, Huiyao Shi, Kaixuan Wang, Jialin Shi, Chanmin Su, Yuanjin Zhao, Lianqing Liu","doi":"10.1002/agt2.614","DOIUrl":"https://doi.org/10.1002/agt2.614","url":null,"abstract":"Cardiac diseases threaten human health and burden the global healthcare system. Cardiomyocytes (CMs) are considered the ideal model for studying the signal transduction and regulation of cardiac systems. Based on the principle of the rhythmical beating process (excitation‒contraction coupling mechanism of CMs), investigating the mechanical and electrophysiological signals offered new hope for cardiac disease detection, prevention, and treatment. Considerable technological success has been achieved in electromechanical signal recording. However, most drug assessment platforms attach importance to high‐throughput and dynamic monitoring of mechanical or electrical signals while overlooking the measuring principles and physiological significance of the signal. In this review, the development of biosensing platforms for CMs, sensing principles, key measured parameters, measurement accuracy, and limitations are discussed. Additionally, various approaches for the stimulation and measurement of CMs in vitro are discussed to further elucidate the response of these cells to external stimuli. Furthermore, disease modeling and drug screening are used as examples to intuitively demonstrate the contribution of in vitro CM measurement platforms to the biomedical field, thereby further illustrating the challenges and prospects of these sensing platforms.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141513765","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}
Advancements in organic electronics are propelling the development of new material systems, where organic materials stand out for their unique benefits, including tunability and cost‐effectiveness. Organic single crystals stand out for their ordered structure and reduced defects, enhancing the understanding of the relationship between structure and performance. Organic cocrystal engineering builds upon these foundations, exploring intermolecular interactions within multicomponent‐ordered crystalline materials to combine the inherent advantages of single‐component crystals. However, the path to realizing the full potential of organic cocrystals is fraught with challenges, including structural mismatches, unclear cocrystallization mechanisms, and unpredictable property alterations, which complicate the effective cocrystallization between different molecules. To deepen the understanding of this promising area, this review introduces the mechanism of organic cocrystal formation, the various stacking modes, and different growth techniques, and highlights the advancements in cocrystal engineering for multifunctional applications. The goal is to provide comprehensive guidelines for the cocrystal engineering of high‐performance molecular materials, thereby expanding the applications of organic cocrystals in the fields of optoelectronics, photothermal energy, and energy storage and conversion.
{"title":"Organic cocrystals: From high‐performance molecular materials to multi‐functional applications","authors":"Yuqing Ding, Yan Zhao, Yunqi Liu","doi":"10.1002/agt2.626","DOIUrl":"https://doi.org/10.1002/agt2.626","url":null,"abstract":"Advancements in organic electronics are propelling the development of new material systems, where organic materials stand out for their unique benefits, including tunability and cost‐effectiveness. Organic single crystals stand out for their ordered structure and reduced defects, enhancing the understanding of the relationship between structure and performance. Organic cocrystal engineering builds upon these foundations, exploring intermolecular interactions within multicomponent‐ordered crystalline materials to combine the inherent advantages of single‐component crystals. However, the path to realizing the full potential of organic cocrystals is fraught with challenges, including structural mismatches, unclear cocrystallization mechanisms, and unpredictable property alterations, which complicate the effective cocrystallization between different molecules. To deepen the understanding of this promising area, this review introduces the mechanism of organic cocrystal formation, the various stacking modes, and different growth techniques, and highlights the advancements in cocrystal engineering for multifunctional applications. The goal is to provide comprehensive guidelines for the cocrystal engineering of high‐performance molecular materials, thereby expanding the applications of organic cocrystals in the fields of optoelectronics, photothermal energy, and energy storage and conversion.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141513766","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}
Chirality in confined nanospaces has brought some new insights into chirality transfer, amplification, and chiroptical properties. However, chirality switching, which is a common phenomenon in biological systems, has never been realized in confined environments. Herein, we report a type of hexagonal metallacages that shows good host–guest interactions with ethoxy pillar[5]arene and pillar[6]arene, as confirmed by single‐crystal X‐ray analysis. Importantly, when a chiral pillar[5]arene‐based molecular universal joint (MUJ) is used as the guest, the host–guest complexation would drive the alkyl ring of the MUJ flip from outside to inside the cavity of its pillar[5]arene unit, which enables the configuration change along with the chirality inversion of the MUJ. Moreover, the host–guest complexation facilitates the chirality transfer from guests to hosts, giving circularly polarized luminescence to the system. This study provides a unique metallacage‐pillararene recognition motif for the chirality switching of planar chiral pillararenes, which will promote the construction of host–guest systems with tunable chirality for advanced applications.
密闭纳米空间中的手性为手性传递、放大和自旋特性带来了一些新的见解。然而，生物系统中常见的手性转换现象却从未在密闭环境中实现过。在此，我们报告了一种六方金属离子，它与乙氧基支柱[5]炔和支柱[6]炔之间表现出良好的主客相互作用，这一点已被单晶 X 射线分析所证实。重要的是，当手性支柱[5]炔基分子万能接头（MUJ）被用作客体时，主-客复合物会促使 MUJ 的烷基环从其支柱[5]炔单元的空腔外侧翻转到空腔内侧，从而实现构型的改变以及 MUJ 的手性反转。此外，宿主-客体复合还促进了客体到宿主的手性转移，从而使该体系发出圆偏振光。这项研究为平面手性柱状烯的手性转换提供了一种独特的金属-柱状烯识别图案，这将促进具有可调手性的宿主-客体系统的构建，从而推动其在先进应用领域的发展。
{"title":"Host–guest complexation‐induced chirality switching of pillararenes by perylene diimide‐based hexagonal metallacages","authors":"Yali Hou, Chaoqun Mu, Yunzhi Shi, Zeyuan Zhang, Haifei Liu, Zilin Zhou, Sanliang Ling, Bingbing Shi, Xianglong Duan, Cheng Yang, Mingming Zhang","doi":"10.1002/agt2.628","DOIUrl":"https://doi.org/10.1002/agt2.628","url":null,"abstract":"Chirality in confined nanospaces has brought some new insights into chirality transfer, amplification, and chiroptical properties. However, chirality switching, which is a common phenomenon in biological systems, has never been realized in confined environments. Herein, we report a type of hexagonal metallacages that shows good host–guest interactions with ethoxy pillar[5]arene and pillar[6]arene, as confirmed by single‐crystal X‐ray analysis. Importantly, when a chiral pillar[5]arene‐based molecular universal joint (MUJ) is used as the guest, the host–guest complexation would drive the alkyl ring of the MUJ flip from outside to inside the cavity of its pillar[5]arene unit, which enables the configuration change along with the chirality inversion of the MUJ. Moreover, the host–guest complexation facilitates the chirality transfer from guests to hosts, giving circularly polarized luminescence to the system. This study provides a unique metallacage‐pillararene recognition motif for the chirality switching of planar chiral pillararenes, which will promote the construction of host–guest systems with tunable chirality for advanced applications.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141551770","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 life‐threatening colorectal cancer exhibits multilevel immunosuppressive characteristics, including low immunogenicity, abnormal cellular metabolism, and acidic immunosuppressive microenvironment. In this work, multi‐synergistic chemotherapeutic drug assemblies are fabricated to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics. Without any drug excipients, the glycolysis inhibitor of lonidamine (LON), indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor of NLG919 (NLG), and the photosensitizer of chlorine e6 could self‐assemble into drug assemblies (LNC) with uniform nano‐size distribution and increased drug stability. Moreover, LNC could also promote cellular uptake and enhance drug penetration to enable efficient drug co‐delivery. Especially, the photodynamic therapy (PDT) of LNC could disrupt tumor cells to release tumor‐associated antigens, thus efficiently suppressing primary tumor growth and improving tumor immunogenicity. Meanwhile, LNC could also reduce the activity of IDO‐1 and attenuate the glycolysis metabolism, thereby reversing the multilevel immunosuppressive characteristics to promote T cell activation. Benefiting from the multi‐synergistic effects, LNC efficiently eradicates the primary tumor growth and also activates systemic antitumor immunity for metastatic tumor inhibition. Such a simple formulation but a multi‐synergistic strategy may accelerate the development of translational nanomedicine for colorectal cancer immunotherapy by using small molecular drug combinations.
危及生命的结直肠癌具有多层次的免疫抑制特征，包括免疫原性低、细胞代谢异常和酸性免疫抑制微环境。在这项工作中，通过调节多层次免疫抑制特性，制备了多重协同化疗药物组合物，以激活结直肠癌免疫疗法。在不添加任何药物辅料的情况下，糖酵解抑制剂洛尼达明（LON）、吲哚胺-2,3-二氧合酶1（IDO-1）抑制剂NLG919（NLG）和光敏剂氯e6可自组装成药物组合物（LNC），其纳米尺寸分布均匀，药物稳定性增强。此外，LNC 还能促进细胞吸收并增强药物渗透，从而实现高效的药物协同递送。特别是，LNC 的光动力疗法（PDT）可以破坏肿瘤细胞，释放肿瘤相关抗原，从而有效抑制原发性肿瘤的生长，提高肿瘤的免疫原性。同时，LNC 还能降低 IDO-1 的活性，减弱糖酵解代谢，从而逆转多级免疫抑制特性，促进 T 细胞活化。得益于多重协同作用，LNC 不仅能有效根除原发性肿瘤的生长，还能激活全身抗肿瘤免疫，抑制转移性肿瘤。这种配方简单但具有多重协同作用的策略可能会加速利用小分子药物组合进行结直肠癌免疫治疗的转化纳米药物的开发。
{"title":"Multi‐synergistic chemotherapeutic drug assemblies to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics","authors":"Rongrong Zheng, Chuyu Huang, Hangyu Zhou, Lixin Zhao, Qiuyuan Li, Guangmiao Chen, Linping Zhao, Shiying Li","doi":"10.1002/agt2.610","DOIUrl":"https://doi.org/10.1002/agt2.610","url":null,"abstract":"The life‐threatening colorectal cancer exhibits multilevel immunosuppressive characteristics, including low immunogenicity, abnormal cellular metabolism, and acidic immunosuppressive microenvironment. In this work, multi‐synergistic chemotherapeutic drug assemblies are fabricated to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics. Without any drug excipients, the glycolysis inhibitor of lonidamine (LON), indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor of NLG919 (NLG), and the photosensitizer of chlorine e6 could self‐assemble into drug assemblies (LNC) with uniform nano‐size distribution and increased drug stability. Moreover, LNC could also promote cellular uptake and enhance drug penetration to enable efficient drug co‐delivery. Especially, the photodynamic therapy (PDT) of LNC could disrupt tumor cells to release tumor‐associated antigens, thus efficiently suppressing primary tumor growth and improving tumor immunogenicity. Meanwhile, LNC could also reduce the activity of IDO‐1 and attenuate the glycolysis metabolism, thereby reversing the multilevel immunosuppressive characteristics to promote T cell activation. Benefiting from the multi‐synergistic effects, LNC efficiently eradicates the primary tumor growth and also activates systemic antitumor immunity for metastatic tumor inhibition. Such a simple formulation but a multi‐synergistic strategy may accelerate the development of translational nanomedicine for colorectal cancer immunotherapy by using small molecular drug combinations.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141551769","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 poor prognosis of triple‐negative breast cancer (TNBC) results from its high metastasis, whereas inflammation accompanied by excessive reactive oxygen species (ROS) is prone to aggravate tumor metastasis. Although photothermal therapy (PTT) has extremely high therapeutic efficiency, the crafty tumor cells allow an increase in the expression of heat shock proteins (HSPs) to limit its effect, and PTT‐induced inflammation is also thought to be a potential trigger for tumor metastasis. Herein, myricetin, iron ions, and polyvinylpyrrolidone were utilized to develop nanomedicines by self‐assembly strategy for the treatment of metastatic TNBC. The nanomedicines with marvelous water solubility and dispersion can inhibit glucose transporter 1 and interfere with mitochondrial function to block the energy supply of tumor cells, achieving starvation therapy on TNBC cells. Nanomedicines with excellent photothermal conversion properties allow down‐regulating the expression of HSPs to enhance the effect of PTT. Interestingly, the broad spectrum of ROS scavenging ability of nanomedicines successfully attenuates PTT‐induced inflammation as well as influences hypoxia‐inducible factors‐1α/3‐phosphoinositide‐dependent protein kinase 1 related pathway through glycometabolism inhibition to reduce tumor cell metastasis. Moreover, the nanomedicines have negligible side effects and good clinical application prospects, which provides a valuable paradigm for the treatment of metastatic TNBC through glycometabolism interference, anti‐inflammation, starvation, and photothermal synergistic therapy.
三阴性乳腺癌（TNBC）预后不良的原因是其转移率较高，而炎症伴随着过多的活性氧（ROS）容易加重肿瘤的转移。虽然光热疗法（PTT）具有极高的治疗效率，但狡猾的肿瘤细胞会使热休克蛋白（HSPs）的表达增加，从而限制了光热疗法的效果，而PTT诱发的炎症也被认为是肿瘤转移的潜在诱因。本文利用三尖杉酯素、铁离子和聚乙烯吡咯烷酮，通过自组装策略开发出治疗转移性 TNBC 的纳米药物。纳米药物具有良好的水溶性和分散性，能抑制葡萄糖转运体1，干扰线粒体功能，阻断肿瘤细胞的能量供应，实现对TNBC细胞的饥饿治疗。具有优异光热转换特性的纳米药物可以下调 HSPs 的表达，从而增强 PTT 的效果。有趣的是，纳米药物的广谱 ROS 清除能力成功地减轻了 PTT 诱导的炎症反应，并通过抑制糖代谢影响了缺氧诱导因子-1α/3-磷酸肌酸依赖性蛋白激酶 1 的相关通路，从而减少了肿瘤细胞的转移。此外，该纳米药物的副作用微乎其微，具有良好的临床应用前景，为通过糖代谢干扰、抗炎、饥饿和光热协同治疗转移性 TNBC 提供了一种有价值的范式。
{"title":"A self‐assembled nanomedicine for glucose supply interruption‐amplified low‐temperature photothermal therapy and anti‐prometastatic inflammatory processes of triple‐negative breast cancer","authors":"Mingcheng Wang, Huixi Yi, Zhixiong Zhan, Zitong Feng, Gang‐Gang Yang, Yue Zheng, Dong‐Yang Zhang","doi":"10.1002/agt2.622","DOIUrl":"https://doi.org/10.1002/agt2.622","url":null,"abstract":"The poor prognosis of triple‐negative breast cancer (TNBC) results from its high metastasis, whereas inflammation accompanied by excessive reactive oxygen species (ROS) is prone to aggravate tumor metastasis. Although photothermal therapy (PTT) has extremely high therapeutic efficiency, the crafty tumor cells allow an increase in the expression of heat shock proteins (HSPs) to limit its effect, and PTT‐induced inflammation is also thought to be a potential trigger for tumor metastasis. Herein, myricetin, iron ions, and polyvinylpyrrolidone were utilized to develop nanomedicines by self‐assembly strategy for the treatment of metastatic TNBC. The nanomedicines with marvelous water solubility and dispersion can inhibit glucose transporter 1 and interfere with mitochondrial function to block the energy supply of tumor cells, achieving starvation therapy on TNBC cells. Nanomedicines with excellent photothermal conversion properties allow down‐regulating the expression of HSPs to enhance the effect of PTT. Interestingly, the broad spectrum of ROS scavenging ability of nanomedicines successfully attenuates PTT‐induced inflammation as well as influences hypoxia‐inducible factors‐1α/3‐phosphoinositide‐dependent protein kinase 1 related pathway through glycometabolism inhibition to reduce tumor cell metastasis. Moreover, the nanomedicines have negligible side effects and good clinical application prospects, which provides a valuable paradigm for the treatment of metastatic TNBC through glycometabolism interference, anti‐inflammation, starvation, and photothermal synergistic therapy.","PeriodicalId":501414,"journal":{"name":"Aggregate","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141513768","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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