The concept of aggregation‐induced emission (AIE) has opened new opportunities in many research fields. Motivated by the unique feature of AIE fluorogens (AIEgens), during the past decade, many AIE ...molecular probes and AIE nanoparticle (NP) probes have been developed for sensing, imaging and theranostic applications with excellent performance outperforming conventional fluorescent probes. This Review summarizes the latest advancement of AIE molecular probes and AIE NP probes and their emerging biomedical applications. Special focus is to reveal how the AIE probes are evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications via fluorescence imaging, photoacoustic imaging and image‐guided photodynamic/photothermal therapy. The outlook discusses the challenges and future opportunities for AIEgens to advance the biomedical field.
Fluorogens with aggregation‐induced emission (AIEgens) have stimulated the development of AIE molecular probes and AIE nanoparticle probes for various biomedical applications. This Review reveals how the AIE probes have evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications.
Multiplexed cellular organelle imaging using single wavelength excitation is highly desirable for unravelling cellular functions but remains challenging. This requires the design of organelle ...specific fluorophores with distinct emission but similar absorption. Herein, we present two unique aggregation-induced emission (AIE) probes to track mitochondria and lysosomes simultaneously with emission colors that can be distinguished from that of the nucleus stain Hoechst 33342 upon single wavelength excitation. Compared to conventional organelle stains, the two AIE probes have larger Stokes shifts and higher photostability, which endow them with the capability to monitor bioprocesses, such as mitophagy with strong and sustained fluorescent signals. Moreover, both probes can also stain intracellular organelles in zebrafish larvae with good cell-penetrating capabilities, showing their great potential to monitor bioprocesses
.
This article reveals the flux leakage design and modeling principle of a flux leakage controllable permanent magnet (FLC-PM) machine by considering driving cycles. The key is to obtain the ...relationship between flux leakage characteristics and multiple operating conditions. Based on the flux leakage controllable concept, an FLC-PM machine with an artfully designed flux leakage region is proposed. The design principle of the machine is investigated by analyzing the magnetic circuit of the machine in multiple operating conditions. The flux leakage factor is introduced to characterize the variable magnetic field in multiple operating conditions. On this basis, the mathematical model of the FLC-PM machine is deduced, and the driving characteristics of the machine are studied in detail. In order to evaluate the presented principle of the FLC-PM machine, a prototype is manufactured for experiments. Through the theoretical analysis and experimental testing, it is verified that the proposed principle is feasible and effective.
Due to the characteristics of inductance parameter mismatch and back electromotive force harmonics caused by novel leakage flux branches and other non-ideal factors for the variable-leakage-flux ...permanent magnet (VLF-PM) motor, its control system suffers from a deteriorated performance of the rotor position estimation. To overcome the problems mentioned above, an adaptive tracking estimator of the rotor position is proposed in this paper for the VLF-PM motor control system. First, the proposed method simplifies the VLF-PM motor mathematical model and reduces the effect of inductance parameter variations according to the active flux concept. Then, robust and gradient descent algorithms are utilized to maintain the robustness of inductance parameter variations and eliminate the specific order harmonics owing to the novel leakage flux branches. Meanwhile, the accuracy and stability are enhanced. Furthermore, the position compensation based on the current adaptive tracking strategy is proposed to compensate the rotor position error caused by other non-ideal factors. Finally, the feasibility of the proposed estimated system is verified.
Transferrin receptor (TfR) represents a unique target for specific imaging of cancer cells and targeted delivery of therapeutic reagents. Detection and qualification of TfR is thus of great ...importance for cancer diagnosis and therapy. In this contribution, a light-up probe TPETH-2T7 was developed by conjugating a red-emissive photosensitizer with aggregation-induced emission (AIE) characteristics to a TfR-targeting peptide T7. The probe is almost nonemissive by itself, but it gives turn-on fluorescence in the presence of TfR with a detection limit of 0.45 μg/mL. Cellular experiments show that the probe specifically binds to TfR-overexpressed cancer cells. Real-time imaging results reveal that the probe stains the MDA-MB-231 cell membrane in 30 min, which is followed by probe internalization. Experiments on image-guided photodynamic cancer ablation show that the therapeutic performance is better when TPETH-2T7 is localized on the cell membrane as compared to that being internalized into cells. Confocal laser scanning microscopy (CLSM) study reveals that cytomembrane disintegration allows quick ablation of MDA-MB-231 cells.
A magnetic bead (MB)-based sandwich biorecognition reactions is combined with a gold nanoprobe-induced homogenous synthesis of molybdophosphate to develop a novel bioassay method for the ...electrochemical detection of the tumor biomarker of carcinoembryonic antigen (CEA). The nanoprobe is prepared through the specific loading of numerous alkaline phosphatase (ALP)-functionalized gold nanoparticles (Au NPs) on a double-stranded DNA (dsDNA) produced by the CEA aptamer-triggered hybridization chain reaction (HCR). Both the large amounts of PO
4
3−
produced by the ALP catalytic hydrolysis of pyrophosphate and the phosphate backbones of dsDNA can react with the added MoO
4
2−
to generate electroactive molybdophosphates. So, the gold nanoprobe was used for signal tracing of the sandwich bioassay of CEA at a constructed antibody-functionalized MB platform. The sensitive electrochemical measurement of molybdophosphate produced from the quantitatively captured nanoprobes at a carbon nanotube-modified electrode (measured at about 0.12 V vs. Ag/AgCl, 3 M KCl) enabled the convenient signal transduction of the method. Due to the dually enhanced synthesis of molybdophosphate by the HCR and multi-enzyme Au NP nanotags, this method shows a wide linear range from 0.05 pg mL
−1
to 10 ng mL
−1
along with a low detection limit of 0.027 pg mL
−1
. In addition, the MB-based biorecognition reaction and the homogeneous synthesis of molybdophosphate are much convenient in manipulations. These excellent performances decide the extensive application potentials of the method.
Graphical abstract
A magnetic bead-based bioassay method was simply developed for the electrochemical detection of carcinoembryonic antigen. The dually enhanced homogenous synthesis of molybdophosphate by hybridization chain reaction (HCR) and enzyme nanotags and the sensitive electrochemical measurement of molybdophosphate at a carbon nanotube (CNT)-electrode enable ultrasensitive signal transduction of the method.
The concept of aggregation‐induced emission (AIE) has opened new opportunities in many research fields. Motivated by the unique feature of AIE fluorogens (AIEgens), during the past decade, many AIE ...molecular probes and AIE nanoparticle (NP) probes have been developed for sensing, imaging and theranostic applications with excellent performance outperforming conventional fluorescent probes. This Review summarizes the latest advancement of AIE molecular probes and AIE NP probes and their emerging biomedical applications. Special focus is to reveal how the AIE probes are evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications via fluorescence imaging, photoacoustic imaging and image‐guided photodynamic/photothermal therapy. The outlook discusses the challenges and future opportunities for AIEgens to advance the biomedical field.
Fluorogens with aggregation‐induced emission (AIEgens) have stimulated the development of AIE molecular probes and AIE nanoparticle probes for various biomedical applications. This Review reveals how the AIE probes have evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications.
The outbreak of 2019 coronavirus disease (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has resulted in a global pandemic. Despite intensive research, the current ...treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS‐CoV‐2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high‐affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS‐CoV‐2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS‐CoV‐2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS‐CoV‐2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS‐CoV‐2 and its variants.
A multifunctional neutralizing antibody‐conjugated nanoparticle is developed to capture and inactivate SARS‐CoV‐2. It efficiently captures SARS‐CoV‐2 pseudovirions and completely blocks viral infection of host cells in vitro through the surface neutralizing antibodies. In addition, its photothermal function inactivates viruses upon light irradiation. More importantly, it treats authentic SARS‐CoV‐2 infection in vivo outperforming neutralizing antibodies.
Bioorthogonal turn‐on probes have been widely utilized in visualizing various biological processes. Most of the currently available bioorthogonal turn‐on probes are blue or green emissive ...fluorophores with azide or tetrazine as functional groups. Herein, we present an alternative strategy of designing bioorthogonal turn‐on probes based on red‐emissive fluorogens with aggregation‐induced emission characteristics (AIEgens). The probe is water soluble and non‐fluorescent due to the dissipation of energy through free molecular motion of the AIEgen, but the fluorescence is immediately turned on upon click reaction with azide‐functionalized glycans on cancer cell surface. The fluorescence turn‐on is ascribed to the restriction of molecular motion of AIEgen, which populates the radiative decay channel. Moreover, the AIEgen can generate reactive oxygen species (ROS) upon visible light (λ=400–700 nm) irradiation, demonstrating its dual role as an imaging and phototherapeutic agent.
Fast and specific: A bioorthogonal turn‐on probe based on a red‐emissive fluorogen with aggregation‐induced emission characteristics (AIEgen) was developed for cancer cell imaging and photodynamic ablation. The fluorescence is immediately turned on upon click reaction with azide‐functionalized glycans on a cancer cell surface.
Bio‐orthogonal tumor labeling is more effective in delivering imaging agents or drugs to a tumor site than active targeting strategy owing to covalent ligation. However, to date, tumor‐specific ...imaging through bio‐orthogonal labeling largely relies on body clearance to differentiate target from the intrinsic probe signal owing to the lack of light‐up probes for in vivo bio‐orthogonal labeling. Now the first light‐up probe based on a fluorogen with aggregation‐induced emission for in vivo bio‐orthogonal fluorescence turn‐on tumor labeling is presented. The probe has low background fluorescence in aqueous media, showing negligible non‐specific interaction with normal tissues. Once it reacts with azide groups introduced to tumor cells through metabolic engineering, the probe fluorescence is lightened up very quickly, enabling rapid tumor‐specific imaging. The photosensitizing ability was also used to realize effective image‐guided photodynamic tumor therapy.
Seeing the light: A bio‐orthogonal light‐up probe based on aggregation‐induced emission is designed to achieve rapid tumor‐specific turn‐on imaging and image‐guided photodynamic tumor therapy.
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