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Fluorescence Imaging and Photodynamic Inactivation of Bacteria Based on Cationic Cyclometalated Iridium(III) Complexes with Aggregation-Induced Emission Properties (Adv. Healthcare Mater. 24/2021)
Po-Yu Ho,Sin-Ying Lee,Chuen Kam,Junfei Zhu,Guo-Gang Shan,Yuning Hong,Wai-Yeung Wong,Sijie Chen
doi : 10.1002/adhm.202170116
Volume 10, Issue 24 2170116
Boosting Photothermal Theranostics via TICT and Molecular Motions for Photohyperthermia Therapy of Muscle-Invasive Bladder Cancer (Adv. Healthcare Mater. 24/2021)
Sheng Zeng,Heqi Gao,Chuang Li,Shaoqiang Xing,Zhaoliang Xu,Qian Liu,Guangxue Feng,Dan Ding
doi : 10.1002/adhm.202170118
Volume 10, Issue 24 2170118
Advances in Improving Healthcare with Aggregation-Induced Emission
Dan Ding,Ben Zhong Tang
doi : 10.1002/adhm.202102499
Volume 10, Issue 24 2102499
Aggregation-Induced Emission-Based Platforms for the Treatment of Bacteria, Fungi, and Viruses
Xiaohui Chen,Haijie Han,Zhe Tang,Qiao Jin,Jian Ji
doi : 10.1002/adhm.202100736
Volume 10, Issue 24 2100736
The prevention and control of pathogenic bacteria, fungi, and viruses is a herculean task for all the countries since they greatly threaten global public health. Rapid detection and effective elimination of these pathogens is crucial for the treatment of related diseases. It is urgently demanded to develop new diagnostic and therapeutic strategies to combat bacteria, fungi, and viruses-induced infections. The emergence of aggregation-induced emission (AIE) luminogens (AIEgens) is a revolutionary breakthrough for the treatment of many diseases, including pathogenic infections. In this review, the main focus is on the applications of AIEgens for theranostic treatment of pathogenic bacteria, fungi, and viruses. Due to the AIE characteristic, AIEgens are promising fluorescent probes for the detection of bacteria, fungi, and viruses with excellent sensitivity and photostability. Moreover, AIEgen-based theranostic platforms can be fabricated by introducing bactericidal moieties or designing AIE photosensitizers and AIE photothermal agents. The current strategies and ongoing developments of AIEgens for the treatment of pathogenic bacteria, fungi, and viruses will be discussed in detail.
AIEgens for Bacterial Imaging and Ablation
Qinggele Borjihan,Haixia Wu,Alideertu Dong,Hui Gao,Ying-Wei Yang
doi : 10.1002/adhm.202100877
Volume 10, Issue 24 2100877
Accurate and sensitive diagnosis of pathogenic bacterial infection is a fundamental first step for correct bacteria management, helping to avoid the development of drug-resistant bacteria caused by the inappropriate use and overuse of antibiotics. Fluorescence probes as a promising visual tool can help identify pathogens rapidly and reliably. However, rigidly structured traditional fluorescence probes generally suffer from the drawback of aggregation-caused quenching (ACQ) effect, which greatly undermines their advantages with respect to sensitivity. Luminogens with aggregation-induced emission properties, namely AIEgens, can overcome the ACQ effect and certain AIEgen-based materials are capable of generating reactive oxygen species (ROS) in the aggregate states. Hence, they have become powerful tools for imaging and killing bacteria. This review summarizes the recent advances in AIEgens for the diagnosis and treatment of pathogen infections. Special attention has been paid to the molecular design, the application in bacterial imaging and ablation in vitro and in vivo, and the biocompatibility of AIEgens. Finally, the challenges and prospects are discussed in terms of using AIEgens to advance precision therapies for pathogen infections.
Practicable Applications of Aggregation-Induced Emission with Biomedical Perspective
Yuqing Wang,Bozhang Xia,Qianqian Huang,Ting Luo,Yuanyuan Zhang,Peter Timashev,Weisheng Guo,Fangzhou Li,Xing-Jie Liang
doi : 10.1002/adhm.202100945
Volume 10, Issue 24 2100945
Considerable efforts have been made into developing aggregation-induced emission fluorogens (AIEgens)-containing nano-therapeutic systems due to the excellent properties of AIEgens. Compared to other fluorescent molecules, AIEgens have advantages including low background, high signal-to-noise ratio, good sensitivity, and resistance to photobleaching, in addition to being exempt from concentration quenching or aggregation-caused quenching effects. The present review outlines the major developments in the biomedical applications of AIEgens-containing systems. From a literature survey, the recent AIE works are reviewed and the reasons why AIEgens are chosen in various biomedical applications are highlighted. The research activities on AIEgens-containing systems are increasing rapidly, therefore, the present review is timely.
PEG-Polymer Encapsulated Aggregation-Induced Emission Nanoparticles for Tumor Theranostics
Jun Dai,Xiaoqi Dong,Quan Wang,Xiaoding Lou,Fan Xia,Shixuan Wang
doi : 10.1002/adhm.202101036
Volume 10, Issue 24 2101036
In the field of tumor imaging and therapy, the aggregation-caused quenching (ACQ) effect of fluorescent dyes at high concentration is a great challenge. In this regard, the aggregation-induced emission luminogens (AIEgens) show great potential, since AIEgens effectively overcome the ACQ effect and have better fluorescence quantum yield, photobleaching resistance, and photosensitivity. Polyethylene glycol (PEG)-polymer is the most commonly used carrier to prepare nanoparticles (NPs). The advantage of PEGylation is that it can greatly prolong the metabolic half-life and reduce immunogenicity and toxicity. Considering that the hydrophobicity of most AIEgens hinders their application in organisms, the use of PEG-polymer encapsulation is an effective strategy to overcome this obstacle. Importantly, bioactive functional groups can be modified on PEG-polymers to enhance the biological effect of NPs. The combination of powerful AIEgens and PEG-polymers provides a new strategy for tumor imaging and therapy, which is promising for clinical application.
Recent Advances in Aggregation-Induced Emission Materials and Their Biomedical and Healthcare Applications
Wei He,Tianfu Zhang,Haotian Bai,Ryan T. K. Kwok,Jacky W. Y. Lam,Ben Zhong Tang
doi : 10.1002/adhm.202101055
Volume 10, Issue 24 2101055
The emergence of the concept of aggregation-induced emission (AIE) has opened new opportunities in many research areas, such as biopsy analysis, biological processes monitoring, and elucidation of key physiological and pathological behaviors. As a new class of luminescent materials, AIE luminogens (AIEgens) possess many prominent advantages such as tunable molecular structures, high molar absorptivity, high brightness, large Stokes shift, excellent photostability, and good biocompatibility. The past two decades have witnessed a dramatic growth of research interest in AIE, and many AIE-based bioprobes with excellent performance have been widely explored in biomedical fields. This review summarizes some of the latest advancements of AIE molecular probes and AIE nanoparticles (NPs) with regards to biomedical and healthcare applications. According to the research areas, the review is divided into five sections, which are imaging and identification of cells and bacteria, photodynamic therapy, multimodal theranostics, deep tissue imaging, and fluorescence-guided surgery. The challenges and future opportunities of AIE materials in the advanced biomedical fields are briefly discussed. In perspective, the AIE-based bioprobes play vital roles in the exploration of advanced bioapplications for the ultimate goal of addressing more healthcare issues by integrating various cutting-edge modalities and techniques.
Recent Advances in AIEgen-Based Photodynamic Therapy and Immunotherapy
Menglei Zha,Guang Yang,Yaxi Li,Chen Zhang,Bo Li,Kai Li
doi : 10.1002/adhm.202101066
Volume 10, Issue 24 2101066
Cancer, one of the leading causes of death, has seriously threatened public health. However, there is still a lack of effective treatments. Nowadays, photodynamic therapy (PDT), relying on photosensitizers to trigger the generation of reactive oxygen species (ROS) for killing cancer cells, has been emerging as a noninvasive anti-cancer strategy. To enhance the overall anti-cancer efficacy of PDT, various approaches including molecular design and combination with other therapeutic techniques have been proposed and implemented. Especially, photodynamic immunotherapy that can effectively evoke the body's immune response has attracted much attention. Recently, a class of photosensitizers with aggregation-induced emission (AIE) character have shown unique promises, taking advantage of their profound fluorescence and ROS-generating ability in the aggregation state. Despite the promising results demonstrated by several groups, the associated studies are few and the mechanism of such AIEgen-based photodynamic immunotherapy has not been fully understood. This review discusses the recent advances in the AIEgen-based enhanced PDT with a special focus on the AIE photosensitizers for photodynamic immunotherapy, aiming to inspire more opportunities for in-depth investigation of the working principles in this emerging anti-cancer approach.
Aggregation-Induced Emission Materials that Aid in Pharmaceutical Research
Bingnan Wang,Shanshan Liu,Xiaolin Liu,Rong Hu,Anjun Qin,Ben Zhong Tang
doi : 10.1002/adhm.202101067
Volume 10, Issue 24 2101067
The in situ visualization of drugs can improve the understanding of their pharmacokinetics and mechanisms. Aggregation-induced emission (AIE) materials, which can aid in the visualization of drugs, are gradually being employed in pharmaceutical research due to their excellent fluorescence properties, good biocompatibility, and extremely high sensitivity. Herein, the progress of AIE materials in pharmaceutical research, including AIE carriers for drug delivery, AIE multifunctional prodrugs, and AIE compounds as bioactive reagents for theranostics is briefly described. Moreover, the opportunities and challenges of AIE materials in pharmaceutical research are discussed in depth. It is believed that versatile AIE materials hold great promise for the promotion of pharmacological research and can facilitate significant advancements in clinical fields.
Aggregation-Induced Emission Luminogens with Photoresponsive Behaviors for Biomedical Applications
Jiaqiang Wang,Liyao Zhang,Zhen Li
doi : 10.1002/adhm.202101169
Volume 10, Issue 24 2101169
Fluorescent biomedical materials can visualize subcellular structures and therapy processes in vivo. The aggregation-induced emission (AIE) phenomenon helps suppress the quenching effect in the aggregated state suffered by conventional fluorescent materials, thereby contributing to design strategies for fluorescent biomedical materials. Photoresponsive biomedical materials have attracted attention because of the inherent advantages of light; i.e., remote control, high spatial and temporal resolution, and environmentally friendly characteristics, and their combination with AIE facilitates development of fluorescent molecules with efficient photochemical reactions upon light irradiation. In this review, organic compounds with AIE features for biomedical applications and design strategies for photoresponsive AIE luminogens (AIEgens) are first summarized briefly. Applications are then reviewed, with the employment of photoresponsive and AIE-active molecules for photoactivation imaging, super-resolution imaging, light-induced drug delivery, photodynamic therapy with photochromic behavior, and bacterial targeting and killing being discussed at length. Finally, the future outlook for AIEgens is considered with the aim of stimulating innovative work for further development of this field.
Photoactivatable Biomedical Materials Based on Luminogens with Aggregation-Induced Emission (AIE) Characteristics
Jiangman Sun,Hui Li,Xinggui Gu,Ben Zhong Tang
doi : 10.1002/adhm.202101177
Volume 10, Issue 24 2101177
Fluorescence probes with aggregation-induced emission (AIE) property are fascinating and vital in biological fields due to their bright fluorescence in the solid state. In contrast, traditional AIE materials are obscured by the off-target effects and lack of spatial and temporal control. Photoactivatable materials with AIE characteristics, whose physicochemical behaviors can be remotely activated by light, provide great potential in biochemical information acquisition with high spatial and temporal resolution. By using AIE-featured photoactivatable fluorescence probes, accurate analysis of the targets of interest is possible. For example, where, when, and to what extent a process is started or stopped by manipulating the non-invasive light accurately. Thus, many researchers are enthusiastic about developing AIE-featured photoactivatable materials and mainly focus on developing novel molecules by rational molecular structure design, and exploring advanced applications by appropriate molecular functionalization. In this review, the recent achievements of photoactivatable materials with AIE characteristics from the aspects involving inherent mechanism of photoactivity, molecular design strategy, and the corresponding applications in biological fields, are summarized. The biological applications are highlighted and discussed, including photoactivatable bioimaging, diagnosis, and photo-controlled therapy. Finally, the challenges and prospects of the AIE-featured photoactivatable materials are also outlined and discussed.
Microalgae-Derived Health Supplements to Therapeutic Shifts: Redox-Based Study Opportunities with AIE-Based Technologies
A. H. M. Mohsinul Reza,Xiaochen Zhu,Jianguang Qin,Youhong Tang
doi : 10.1002/adhm.202101223
Volume 10, Issue 24 2101223
Reactive oxygen species (ROS) are highly reactive molecules, serve the normal signaling in different cell types. Targeting ROS as the chemical signals, different stress based strategies have been developed to synthesis different anti-inflammatory molecules in microalgae. These molecules could be utilized as health supplements in human. To provoke the ROS-mediated defence systems, their connotation with the associated conditions must be well understood, therefore, proper tools for studying ROS in natural state are essential. The in vivo detection of ROS with phosphorescent probes offers promising opportunities to study these molecules in a non-invasive manner. Most of the common problems in the traditional fluorescent probes are lower photostability, excitation intensity, slow responsiveness, and the microenvironment that challenge their performance. Some ROS-specific aggregationinduced emission luminogens (AIEgens) with pronounced spatial and temporal resolution have recently demonstrated high selectivity, rapid responsiveness, and efficacies to resolve the aggregation-caused quenching issues. The nanocomposites of some AIE-photosensitizers can also improve the ROS-mediated photodynamic therapy. These AIEgens could be used to induce bioactive components in microalgae through altering the ROS signaling, therefore are more auspicious for biomedical research. This study reviews the prospects of AIEgen-based technologies to understand the ROS mediated bio-physiological processes in microalgae for better healthcare benefits.
Recent Advances in Hypoxia-Overcoming Strategy of Aggregation-Induced Emission Photosensitizers for Efficient Photodynamic Therapy
Huan Chen,Yingpeng Wan,Xiao Cui,Shengliang Li,Chun-Sing Lee
doi : 10.1002/adhm.202101607
Volume 10, Issue 24 2101607
Hypoxia is an inherent physiologic barrier in the microenvironment of solid tumor and has badly restricted the therapeutic effect of photodynamic therapy (PDT). Meanwhile, the photosensitizer (PS) agents used for PDT applications regularly encounter the tiresome aggregation-caused quenching effect that seriously decreases the production efficiency of cytotoxic reactive oxygen species. The aggregation-induced emission (AIE) PSs with antiquenching characteristics in the aggregate state are considered as a promising tool for achieving highly efficient PDT applications, and plenty of studies have widely demonstrated their advantages in various diseases. Herein, the recent progress of AIE PSs in the battle of antitumor hypoxia issue is summarized and the practical molecular principles of hypoxia-overcoming AIE PSs are highlighted. According to the hypoxia-overcoming mechanism, these representative cases are divided into low O2-dependent (type I PDT) and O2-dependent tactics (mainly including O2-enrichment type II PDT and combination therapy). Furthermore, the underlying challenges and prospects of AIE PSs in hypoxia-overcoming PDT are proposed and thus expect to promote the next development of AIE PSs.
Fluorescence Imaging and Photodynamic Inactivation of Bacteria Based on Cationic Cyclometalated Iridium(III) Complexes with Aggregation-Induced Emission Properties
Po-Yu Ho,Sin-Ying Lee,Chuen Kam,Junfei Zhu,Guo-Gang Shan,Yuning Hong,Wai-Yeung Wong,Sijie Chen
doi : 10.1002/adhm.202100706
Volume 10, Issue 24 2100706
Antibacterial photodynamic therapy (PDT) is one of the emerging methods for curbing multidrug-resistant bacterial infections. Effective fluorescent photosensitizers with dual functions of bacteria imaging and PDT applications are highly desirable. In this study, three cationic and heteroleptic cyclometalated Ir(III) complexes with the formula of [Ir(CˆN)2(NˆN)][PF6] are prepared and characterized. These Ir(III) complexes named Ir(ppy)2bP, Ir(1-pq)2bP, and Ir(2-pq)2bP are comprised of three CˆN ligands (i.e., 2-phenylpyridine (ppy), 1-phenylisoquinoline (1-pq), and 2-phenylquinoline (2-pq)) and one NˆN bidentate co-ligand (bP). The photophysical characterizations demonstrate that these Ir(III) complexes are red-emitting, aggregation-induced emission active luminogens. The substitution of phenylpyridine with phenylquinoline isomers in the molecules greatly enhances their UV and visible-light absorbance as well as the photoinduced reactive oxygen species (ROS) generation ability. All three Ir(III) complexes can stain both Gram-positive and Gram-negative bacteria efficiently. Interestingly, even though Ir(1-pq)2bP and Ir(2-pq)2bP are constitutional isomers with very similar structures and similar ROS generation ability in buffer, the former eradicates bacteria much more effectively than the other through white light-irradiated photodynamic inactivation. This work will provide valuable information on the rational design of Ir(III) complexes for fluorescence imaging and efficient photodynamic inactivation of bacteria.
Boosting Photothermal Theranostics via TICT and Molecular Motions for Photohyperthermia Therapy of Muscle-Invasive Bladder Cancer
Sheng Zeng,Heqi Gao,Chuang Li,Shaoqiang Xing,Zhaoliang Xu,Qian Liu,Guangxue Feng,Dan Ding
doi : 10.1002/adhm.202101063
Volume 10, Issue 24 2101063
The development of photothermal agents with high photothermal conversion efficiency (PCE) can help to reduce drug and laser dosage, but still remains a big challenge. Herein, a novel approach is reported to design photothermal agents with high PCE values by promoting nonradiative heat generation processes through the cooperation of twisted intramolecular charge transfer (TICT) and molecular motions. Within the designed molecule 2DMTT-BBTD, the tetraphenylethenes act as molecular rotors, the long alkyl chain grafted thiophene helps to twist the molecular geometry to facilitate TICT state formation and preserve molecular motions in aggregate, while the strong electron-withdrawing BBTD unit enhances TICT effect. 2DMTT-BBTD exhibits NIR-absorption and a high PCE value of 74.8% under 808 nm laser irradiation. Gambogic acid (GA) which surmounts tumor cell thermotolerance by inhibiting heat shock protein 90 (HSP90) expression is coloaded into the nanoparticles, RGD peptide is further introduced to the nanoparticle surface to improve tumor accumulation. The resultant nanoparticles facilitate the effective low-temperature hyperthermia therapy of muscle-invasive bladder cancer (MIBC) with minimal damage to surrounding heathy tissues. This work delivers a new design concept for development of highly efficient photothermal agents, which also provides a safer approach for noninvasive treatment of MIBC and other malignant tumors.
Conformational Transition-Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy
Guo-Qiao Wang,Jia Yang,Da-Yong Hou,Rui Zheng,Muhetaerjiang Mamuti,Min-Jie Guo,Zhi Fan,Hong-Wei An,Hao Wang
doi : 10.1002/adhm.202100333
Volume 10, Issue 24 2100333
Cationic therapeutic peptides have received widespread attention due to their excellent antibacterial and antitumor properties. However, most of these peptides have undesirable delivery efficiency and high hemolytic toxicity due to the positively charged ?-helix structure containing many lysine and arginine, which may restrict its in vivo applications. Herein, a conformationally transformed therapeutic peptide Pep-HCO3 modified with bicarbonates on guanidine groups is designed. Such a design allows Pep-HCO3 ((nap-RAGLQFPVGRLLRRLLRRLLR) nHCO3) to self-assemble into nanoparticles (NP-Pep) due to disrupting helix folding and the formation of intermolecular hydrogen bonding between bicarbonates and guanidine groups. When pH is from 7.4 to 6.5 at the tumor sites, guanidine bicarbonate can be hydrolyzed to form CO2 and guanidine groups, resulting in the disassembling of the NP-Pep into monomers ?-Pep with a positively charged ?-helix structure. In vivo, NP-Pep not only inhibits the tumor growth of xenografted mice with a twofold enhanced inhibition rate compared with ?-Pep treatment group, but also significantly reduces the hemolytic toxicity by responding to the pH of tumor microenvironment. Therefore, the strategy of conformational transition-triggered disassembly of nanoparticles allows efficient delivery of cationic therapeutic peptides and lowering the hemolytic toxicity, which may provide an avenue for developing high-performance cationic peptide in vivo applications.
Surfactant-Stripped Micelles with Aggregation-Induced Enhanced Emission for Bimodal Gut Imaging In Vivo and Microbiota Tagging Ex Vivo
Zhen Jiang,Boyang Sun,Yueqi Wang,Heqi Gao,He Ren,Hao Zhang,Tong Lu,Xiangkui Ren,Wei Wei,Xiaoli Wang,Lei Zhang,Jiao Li,Dan Ding,Jonathan F. Lovell,Yumiao Zhang
doi : 10.1002/adhm.202100356
Volume 10, Issue 24 2100356
Aggregation-induced emission luminogens (AIEgens) hold promise for biomedical imaging and new approaches facilitating their aggregation state are desirable for fluorescence enhancement. Herein, a series of surfactant-stripped AIEgen micelles (SSAMs) with improved fluorescence are developed by a low-temperature surfactant-stripping method to encapsulate AIEgens in temperature-sensitive Pluronic block copolymer. After stripping excessive surfactant, SSAMs exhibit altered optical properties and significantly higher fluorescence quantum yield. Using this method, a library of highly concentrated fluorescent nanoparticles are generated with tunable absorption and emission wavelengths, permitting imaging of deep tissues at different wavelengths. SSAMs remain physiologically stable and can pass safely through gastrointestinal tract (GI) without degradation in the harsh conditions, allowing for fluorescence and photoacoustic imaging of intestine with high resolution. d-amino acids (DAA), a natural metabolite for bacteria, can be chemically conjugated on the surface of SSAMs, enabling non-invasive monitoring of the microbial behavior of ex vivo fluorescently labeled gut microbiota in the GI tract.
Optimizing Comprehensive Performance of Aggregation-Induced Emission Nanoparticles through Molecular Packing Modulation for Multimodal Image-Guided Synergistic Phototherapy
Xian Wang,Luqi Liu,Li-Juan Wang,Lianqin Guo,Yanbin Li,Bing Bai,Fan Fu,Hongguang Lu,Xiaowei Zhao
doi : 10.1002/adhm.202100360
Volume 10, Issue 24 2100360
Fluorescent nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics hold remarkable potential for image-guided phototherapy. The molecular packing is the key point for optimizing the performance of AIE luminogens (AIEgens) in the aggregated or solid state. However, so far, the packing mode of AIEgens in NPs is still vague, causing some challenges for understanding the relationship between the photophysical property and packing mode, as well as further optimizing the performance of NPs for biomedical applications. In this contribution, by simply controlling the length of alkoxy chains in the donor–acceptor conjugated OPTPA, a packing balance between the twisted molecular structure and effective ?-conjugation is actualized. Subsequently, the possibility of amorphous-crystalline transition of AIEgens in the polymer-encapsulated NPs is presented for the first time, and the comprehensive performance of NPs is further optimized. Both in vitro and in vivo experiments indicate that crystalline AIEgen-based NPs are remarkably effective in trimodal imaging-guided synergistic phototherapy.
An Activatable Probe with Aggregation-Induced Emission for Detecting and Imaging Herbal Medicine Induced Liver Injury with Optoacoustic Imaging and NIR-II Fluorescence Imaging
Lihe Sun,Juan Ouyang,Yunqing Ma,Zhuo Zeng,Cheng Zeng,Fang Zeng,Shuizhu Wu
doi : 10.1002/adhm.202100867
Volume 10, Issue 24 2100867
Whilte herbal medicines are widely used for health promotion and therapy for chronic conditions, inappropriate use of them may cause adverse effects like liver injury, and accurately evaluating their hepatotoxicity is of great significance for public health. Herein, an activatable probe QY-N for diagnosing herbal-medicine-induced liver injury by detecting hepatic NO with NIR-II fluorescence and multispectral optoacoustic tomography (MSOT) imaging is demonstrated. The probe includes a bismethoxyphenyl-amine-containing dihydroxanthene serving as electron donor, a quinolinium as electron acceptor, and a butylamine as recognition group and fluorescence quencher. The hepatic level of NO reacts with butylamine, thereby generating the activated probe QY-NO which exhibits a red-shifted absorption band (700–850 nm) for optoacoustic imaging and generates strong emission (910–1110 nm) for NIR-II fluorescence imaging. QY-NO is aggregation-induced-emission (AIE) active, which ensures strong emission in aggregated state. QY-N is utilized in the triptolide-induced liver injury mouse model, and experimental results demonstrate the QY-N can be activated by hepatic NO and thus be used in detecting herbal-medicine-induced liver injury. The temporal and spatial information provided by three-dimensional MSOT images well delineates the site and size of liver injury. Moreover, QY-N has also been employed to monitor rehabilitation of liver injury during treatment process.
An AIEgen as an Intrinsic Antibacterial Agent for Light-Up Detection and Inactivation of Intracellular Gram-Positive Bacteria
Tianjiao Dai,Bingpeng Guo,Guobin Qi,Shidang Xu,Cheng Zhou,Guillermo C. Bazan,Bin Liu
doi : 10.1002/adhm.202100885
Volume 10, Issue 24 2100885
Infections caused by Gram-positive bacteria, especially those able to invade and survive in host cells, threaten human health severely. It is therefore highly desirable to develop therapeutics that can selectively target and kill intracellular Gram-positive pathogens with minimal toxicity to host cells. Herein, it is described that the aggregation-induced emission luminogen (AIEgen) TPEPy-Et, containing a positively charged pyridinium group and a hydrophobic tetraphenylethylene fragment, is effective for Gram-positive bacteria detection and elimination. The fluorescence of TPEPy-Et is greatly enhanced after incubation with Gram-positive bacteria, which can be used to detect and trace the bacteria in cells. TPEPy-Et also shows excellent killing effects against both extracellular and intracellular Gram-positive bacteria through a membrane depolarization mechanism. The luminescent antibacterial agent TPEPy-Et is thus promising for diagnosis and therapy against intracellular bacterial infection.
Photosensitizer with High Efficiency Generated in Cells via Light-Induced Self-Oligomerization of 4,6-Dibromothieno[3,4-b]thiophene Compound Entailing a Triphenyl Phosphonium Group
Lingna Wang,Yanyan Huang,Yingjie Yu,Huifei Zhong,Haihua Xiao,Guanxin Zhang,Deqing Zhang
doi : 10.1002/adhm.202100896
Volume 10, Issue 24 2100896
Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but therapeutic effects suffer from low photosensitizing efficiency and poor retention of photosensitizes in cancer cells. This paper reports the photosensitizers which show absorption and emission in the long-wavelength region and high photosensitizing efficiency can be formed in situ in cells from 4,6-dibromothieno[3,4-b]thiophene derivative (TT-5-P) after white light irradiation. The self-oligomerization of TT-5-P is uptaken in cells upon light irradiation-induced cell apoptosis simultaneously and efficiently. In addition, the formation of oligomers (TT-5-Ps) enhances the retention time in cells remarkably, which is advantageous for boosting the photodynamic therapy efficiency. Moreover, the selectivity toward tumor cells of TT-5-P can be improved obviously via the formation of complex of TT-5-P with albumin. This in situ photoinduced self-oligomerization strategy can be utilized to design effective biomaterials for long-term imaging and improved therapy.
Molecular Design of Ultrabright Semiconducting Polymer Dots with High NIR-II Fluorescence for 3D Tumor Mapping
Yi-Xuan Li,Shih-Po Su,Chou-Hsun Yang,Ming-Ho Liu,Pin-Ho Lo,Yi-Chen Chen,Chao-Ping Hsu,Yi-Jang Lee,Huihua Kenny Chiang,Yang-Hsiang Chan
doi : 10.1002/adhm.202100993
Volume 10, Issue 24 2100993
Fluorescence probes emitting in the second near-infrared (NIR-II, 1000–1700 nm) window with the ability for deep-tissue imaging in mammals herald a new era in surgical methodology. However, the brightness of these NIR-II probes is still far from satisfactory due to their low fluorescence quantum yields (QYs), preventing the observation of high-resolution images such as whole-organ vascular networks in real time. Described here is the molecular engineering of a series of semiconducting polymer dots (Pdots) incorporated with aggregation-induced emission moieties to exhibit the QYs as high as 14% in the NIR-II window. Benefiting from the ultrahigh brightness, a 1400 nm long-pass filter is utilized to realize in vivo 3D tumor mapping in mice. To further understand how the geometrical and electron structures of the semiconducting polymers affect their optical properties, the in-depth and thorough density-functional theory calculations are performed to interpret the experimental results. This study lays the groundwork for further molecular design of highly bright NIR-II Pdots.
Aggregation-Induced Emission (AIE) Nanoparticles-Assisted NIR-II Fluorescence Imaging-Guided Diagnosis and Surgery for Inflammatory Bowel Disease (IBD)
Xiaoxiao Fan,Qiming Xia,Yiyin Zhang,Yirun Li,Zhe Feng,Jing Zhou,Ji Qi,Ben Zhong Tang,Jun Qian,Hui Lin
doi : 10.1002/adhm.202101043
Volume 10, Issue 24 2101043
The incidence of inflammatory bowel diseases (IBD), including Crohn's diseases and ulcerative colitis, is increasing by time and showing a trend of younger age. Precise diagnosis and effective treatments for IBD have attracted growing attention in recent years. However, diagnosing and locating inflammatory lesions remain a great challenge for IBD. In this study, assisted by a kind of aggregation-induced emission (AIE) nanoprobes (BPN-BBTD nanoparticles [NPs]), the second near-infrared (NIR-II) fluorescence imaging is first utilized to accurately trace inflammatory lesions, monitor inflammation severity and detect the response to the drug intervention in IBD mouse models. Through the advantages of high signal-to-background ratio (SBR) and sharp spatial resolution of bio-imaging in NIR-II region, the NIR-II fluorescence imaging-guided surgery can help to achieve a complete resection of severe inflammatory bowls and a secure surgical anastomosis. In addition, with the help of NIR-II fluorescence wide-field microscopy, the distribution of BPN-BBTD NPs can be directly detected in tissue level and found to be mainly accumulated in mucosa and submucosa layers. This study highlights that AIE NPs-assisted NIR-II fluorescence imaging hold a great potential value for future diagnosis and imaging-guided surgery in IBD.
Mitochondrion-Anchored Photosensitizer with Near Infrared-I Aggregation-Induced Emission for Near Infrared-II Two-Photon Photodynamic Therapy
Zhenyan He,Yuting Gao,Huimin Zhang,Ying Xue,Fanling Meng,Liang Luo
doi : 10.1002/adhm.202101056
Volume 10, Issue 24 2101056
Two-photon photodynamic therapy (2P-PDT) that employs photosensitizers (PSs) with 2P absorption is particularly intriguing in cancer treatment, in that 2P excitation enables precise spatial localization and deep tissue penetration. Here, a donor-?-acceptor PS (named TPBPy) with near infrared (NIR) aggregation-induced emission (AIE) is designed and synthesized for imaging-guided 2P-PDT. The maximal photoluminescence (PL) peak of TPBPy is as high as 720 nm when it is encapsulated in liposomes. Upon 2P irradiation by a laser in NIR-II window (? = 1000 nm), TPBPy exhibits strong NIR-I PL in a multicellular tumor spheroids (MCTSs) model, showing an imaging depth of 210 µm that is significantly higher than upon one-photon irradiation. Moreover, TPBPy localizes specifically on mitochondrion, an important organelle in cell oxidative metabolism and apoptosis. When exposed to the NIR-II irradiation, TPBPy can efficiently generate singlet oxygen (1O2) and trigger cell death. The efficacy of TPBPy-mediated 2P-PDT has also been validated using 4T1 tumor mouse model, the growth of which is significantly suppressed upon NIR-II laser irradiation. TPBPy herein serves as an excellent candidate to suppress deep tumor tissues through NIR-II 2P-PDT, and also renders a new paradigm to construct mitochondrion-anchored AIE luminogens for future cancer theranostic applications.
Aggregation-Induced Emission-Active Poly(phenyleneethynylene)s for Fluorescence and Raman Dual-Modal Imaging and Drug-Resistant Bacteria Killing
Xiang Su,Ruihua Liu,Ying Li,Ting Han,Zhijun Zhang,Niu Niu,Miaomiao Kang,Shuang Fu,Deliang Wang,Dong Wang,Ben Zhong Tang
doi : 10.1002/adhm.202101167
Volume 10, Issue 24 2101167
Poly(phenyleneethynylene) (PPE) is a widely used functional conjugated polymer with applications ranging from organic optoelectronics and fluorescence sensors to optical imaging and theranostics. However, the fluorescence efficiency of PPE in aggregate states is generally not as good as their solution states, which greatly compromises their performance in fluorescence-related applications. Herein, a series of PPE derivatives with typical aggregation-induced emission (AIE) properties is designed and synthesized. In these PPEs, the diethylamino-substituted tetraphenylethene units function as the long-wavelength AIE source and the alkyl side chains serve as the functionalization site. The obtained AIE-active PPEs with large ?-conjugation show strong aggregate-state fluorescence, interesting self-assembly behaviors, inherently enhanced alkyne vibrations in the Raman-silent region of cells, and efficient antibacterial activities. The PPE nanoparticles with good cellular uptake capability can clearly and sensitively visualize the tumor region and residual tumors via their fluorescence and Raman signals, respectively, to benefit the precise tumor resection surgery. After post-functionalization, the obtained PPE-based polyelectrolyte can preferentially image bacteria over mammalian cells and possesses efficient photodynamic killing capability against Gram-positive and drug-resistant bacteria. This work provides a feasible design strategy for developing functional conjugated polymers with multimodal imaging capability as well as photodynamic antimicrobial ability.
Construction of a Highly Sensitive Thiol-Reactive AIEgen-Peptide Conjugate for Monitoring Protein Unfolding and Aggregation in Cells
Soheila Sabouri,Mengjie Liu,Shouxiang Zhang,Bicheng Yao,Hamid Soleimaninejad,Amy A. Baxter,Georgina Armendariz-Vidales,Pramod Subedi,Chong Duan,Xiaoding Lou,Conor F. Hogan,Begoña Heras,Ivan K. H. Poon,Yuning Hong
doi : 10.1002/adhm.202101300
Volume 10, Issue 24 2101300
Impairment of the protein quality control network leads to the accumulation of unfolded and aggregated proteins. Direct detection of unfolded protein accumulation in the cells may provide the possibility for early diagnosis of neurodegenerative diseases. Here a new platform based on a peptide-conjugated thiol-reactive aggregation-induced emission fluorogen (AIEgen), named MI-BTD-P (or D1), for labeling and tracking unfolded proteins in cells is reported. In vitro experiments with model proteins show that the non-fluorescent D1 only becomes highly fluorescent when reacted with the thiol group of free cysteine (Cys) residues on unfolded proteins but not glutathione or folded proteins with buried or surface exposed Cys. When the labeled unfolded proteins form aggregates, D1 fluorescence intensity is further increased, and fluorescence lifetime is prolonged. D1 is then used to measure unfolded protein loads in cells by flow cytometry and track the aggregate formation of the D1 labeled unfolded proteins using confocal microscopy. In combination with fluorescence lifetime imaging technique, the proteome at different folding statuses can be better differentiated, demonstrating the versatility of this new platform. The rational design of D1 demonstrates the outlook of incorporation of diverse functional groups to achieve maximal sensitivity and selectivity in biological samples.
