Nonlight-Driven Aggregation-Induced Emission Luminogens for Bioimaging and Theranostics.

Aggregation-induced emission luminogens (AIEgens) have been prosperously developed and applied in the fields of optical imaging and theranostics since its establishment. Nowadays, AIEgens can fulfill nearly all requirements in optical imaging and theranostics with emission spectra ranging from visible to near-infrared wavelengths. Although a variety of AIEgens with varying wavelengths and functionalities have been continuously designed, their performance is heavily dependent on the use of conventional light sources, such as xenon lamps and lasers, which severely hinder further applications due to limited penetration depth and background autofluorescence in biological tissues.

Heavy Atom Engineering-Mediated Conformational Diversification to Construct Aggregation-Induced NIR-II Emission Luminogens for Cancer Phototheranostics.

Chromophores with emission in the second near-infrared (NIR-II) window have captivated much interest by taking advantage of the reduced light scattering and bio-autofluorescence in this region. However, those conventional construction approaches to NIR-II chromophores inevitably suffer from some unpractically limitations, as well as from undiversified molecular skeletons and stereotyped design philosophy. A concise strategy is reported for developing an NIR-II chromophore, PSeD, through heavy chalcogen atom engineering-induced conformational diversification.

Self-Assembly versus Coassembly: An Amphiphilic NIR-II Aggregation-Induced Emission Luminogen for Phototheranostics of Orthotopic Glioblastoma.

Glioblastoma (GBM) is the most lethal form of malignant brain tumor, known for its high infiltration, aggressiveness, and poor prognosis. Second near-infrared (NIR-II, 1000-1700 nm) phototheranostic agents bring intriguing opportunities for GBM management owing to their noninvasive nature, controllability, and deeper tissue penetration. Herein, an amphiphilic NIR-II luminogen (PEG-TD) with aggregation-induced emission (AIE) characteristics, along with its hydrophobic counterpart (C6-TD), was meticulously synthesized.

NIR-II aggregation-induced emission nanoparticles camouflaged with preactivated macrophage membranes for phototheranostics of pulmonary tuberculosis.

Phototheranostics, which allows simultaneous diagnosis and therapy, offers notable advantages in terms of noninvasiveness, controllability and negligible drug resistance, presenting a promising approach for disease treatment. By integrating second near-infrared (NIR-II, 1,000-1,700 nm) phototheranostic agents characterized by aggregation-induced emission (AIE) and cell membranes with specific targeting capacity, we have developed a versatile type of biomimetic nanoparticle (NP) for precise phototheranostics of pulmonary tuberculosis (TB). Coating the phototheranostic agents with preactivated macrophage membranes results in the formation of biomimetic NPs, which exhibit specific binding to TB through a lesion-pathogen dual-targeting strategy, allowing the accurate detection of Mycobacterium tuberculosis via NIR-II fluorescence imaging and precise photothermal therapy using the irradiation of a 1,064 nm laser.

An AIE-active near-infrared molecular probe for migrasome labeling.

Migrasomes, newly identified organelles, play crucial roles in various physiological and pathological activities, including embryogenesis, immune responses, wound healing, and metastasis of cancer cells. Migrasome visualization is essential for the deep exploration of migrasome biology. Despite the reported labeling methods based on migrasome marker proteins, a simple and convenient method for migrasome labeling is more desirable compared to the complicated transfection technique.

Mechanistic Insights Into NIR-II AIEgens Boosted Multimodal Phototheranostics.

Exploiting single molecular species synchronously affording powerful second near-infrared (NIR-II) fluorescence, superior photoacoustic output, prominent reactive oxygen species generation, and satisfactory photothermal conversion is supremely appealing for phototheranostics, yet remains formidably challenging. In this work, electron donor/π-bridge engineering is implemented on the basis of 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline moiety. The optimal molecule, namely TPATO-TTQ, is demonstrates to exhibit those notable features requested by exceptional phototheranostics, which are systematically elucidated through the depictions of excited-state energy dissipation pathways and the influence of intramolecular motion on the photophysical properties, with assistances of quantum chemical calculation and molecular dynamic simulation.

A tactfully designed photothermal agent collaborating with ascorbic acid for boosting maxillofacial wound healing.

Maxillofacial injuries that may cause severe functional and aesthetic damage require effective and immediate management due to continuous exposure to diverse microbial populations. Moreover, drug resistance, biofilm formation, and oxidative stress significantly impede timely bacterial removal and immune function, making the exploration of advanced materials for maxillofacial wound healing an appealing yet highly challenging task. Herein, a near-infrared photothermal sterilization agent was designed, encapsulated with liposomes and coated with ascorbic acid known for its antioxidant and immune-regulatory functions.

Molecular Engineering of AIE-Active Photosensitizers with High Biosafety for Effect Extracellular Antibacteria.

Developing versatile photosensitizers to actualize selective antibacteria over normal cells presents an appealing yet significantly challenging task. In this study, a novel photosensitizer named DMMA-SCPI is rationally designed and facilely synthesized, which is demonstrated as a type-I photosensitizer featured by aggregation-induced emission tendency. DMMA-SCPI is capable of effectively eliminating both Galanz positive bacteria and Galanz negative bacteria in vitro and in vivo, and showed insignificant injury to normal cells and tissues, probably resulting from its pyridinium halide that has stronger adsorption property on negatively charged bacteria compared to normal cells, as well as its suitable antimicrobial activity.

Advanced Nanoplatform Mediated by CRISPR-Cas9 and Aggregation-Induced Emission Photosensitizers to Boost Cancer Theranostics.

Immunotherapy combined with phototherapy is emerging as a promising strategy to treat omnipotent cancers. In this study, a clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system, aggregation-induced emission (AIE) photosensitizer (PS) and surface coating of polyethylene imine/hyaluronic acid were combined to construct a multifunctional nanoplatform, denoted as TCPH nanoparticles (NPs), for comprehensive cancer theranostics. TCPH NPs are featured by intrinsic functions including efficient reactive oxygen species (ROS) production, good photothermal conversion, programmed death-ligand 1 (PD-L1)-eliminating capability, and effective intracellular transport.

Activatable fluorescent probes for atherosclerosis theranostics.

The onset of atherosclerosis (AS) is insidious, and early stage patients have atypical clinical symptoms. After being diagnosed in late stage, it is often prone to sudden and fatal cardiovascular events. Therefore, it is highly desirable to develop precise and efficient diagnosis and therapy strategies of AS.

NIR-II AIEgens for Infectious Diseases Phototheranostics.

Pathogenic infectious diseases have persistently posed significant threats to public health. Phototheranostics, which combines the functions of diagnostic imaging and therapy, presents an extremely promising solution to block the spread of pathogens as well as the outbreak of epidemics owing to its merits of a wide-spectrum of activity, high controllability, non-invasiveness, and difficult to acquire resistance. Among multifarious phototheranostic agents, second near-infrared (NIR-II, 1000-1700 nm) aggregation-induced emission luminogens (AIEgens) are notable by virtue of their deep penetration depth, excellent biocompatibility, balanced radiative and nonradiative decay and aggregation-enhanced theranostic performance, making them an ideal option for combating pathogens.

Dual-/multi-organelle-targeted AIE probes associated with oxidative stress for biomedical applications.

monitoring of biological processes between different organelles upon oxidative stress is one of the most important research hotspots. Fluorescence imaging is especially suitable for biomedical applications due to its distinct advantages of high spatiotemporal resolution, high sensitivity, non-invasiveness, and monitoring capabilities. However, most fluorescent probes can only achieve light-up imaging of single organelles, thus the combined use of two or more probes is usually required for monitoring biological processes between organelles, which can suffer from tedious staining and washing procedures, increased cytotoxicity and poor photostability.

Structural modulation of aggregation-induced emission luminogens for NIR-II fluorescence imaging/photoacoustic imaging of tumors.

Concurrent near-infrared-II (NIR-II) fluorescence imaging (FLI) and photoacoustic imaging (PAI) holds tremendous potential for effective disease diagnosis owing to their combined benefits and complementary features, in particular on the basis of a single molecule. However, the simultaneous guarantee of high-quality NIR-II FLI and PAI is recognized to be challenging impeded by the competitive photophysical processes at the molecular level. Herein, a simple organic fluorophore, namely T-NSD, is finely engineered with facile synthetic procedures through delicately modulating the rigidity and electron-withdrawing ability of the molecular acceptor.

NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tuberculosis.

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.

Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling.

Recent advances in chemical proteomics have focused on developing chemical probes that react with nucleophilic amino acid residues. Although histidine is an attractive candidate due to its importance in enzymatic catalysis, metal binding and protein-protein interaction, its moderate nucleophilicity poses challenges. Its modification is frequently influenced by cysteine and lysine, which results in poor selectivity and narrow proteome coverage.

An All-Rounder for NIR-II Phototheranostics: Well-Tailored 1064 nm-Excitable Molecule for Photothermal Combating of Orthotopic Breast Cancer.

The second near-infrared (NIR-II, 1000-1700 nm) light-activated organic photothermal agent that synchronously enables satisfying NIR-II fluorescence imaging is highly warranted yet rather challenging on the basis of the overwhelming nonradiative decay. Herein, such an agent, namely TPABT-TD, was tactfully designed and constructed via employing benzo[c]thiophene moiety as bulky electron donor/π-bridge and tailoring the peripheral molecular rotors. Benefitting from its high electron donor-acceptor strength and finely modulated intramolecular motion, TPABT-TD simultaneously exhibits ultralong absorption in NIR-II region, intense fluorescence emission in the NIR-IIa (1300-1500 nm) region as nanoaggregates, and high photothermal conversion upon 1064 nm laser irradiation.

Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles.

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion-pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M.

Thiophene π-Bridge Manipulation of NIR-II AIEgens for Multimodal Tumor Phototheranostics.

The fabrication of a multimodal phototheranostic platform on the basis of single-component theranostic agent to afford both imaging and therapy simultaneously, is attractive yet full of challenges. The emergence of aggregation-induced emission luminogens (AIEgens), particularly those emit fluorescence in the second near-infrared window (NIR-II), provides a powerful tool for cancer treatment by virtue of adjustable pathway for radiative/non-radiative energy consumption, deeper penetration depth and aggregation-enhanced theranostic performance. Although bulky thiophene π-bridges such as ortho-alkylated thiophene, 3,4-ethoxylene dioxythiophene and benzo[c]thiophene are commonly adopted to construct NIR-II AIEgens, the subtle differentiation on their theranostic behaviours has yet to be comprehensively investigated.

Adding Flying Wings: Butterfly-Shaped NIR-II AIEgens with Multiple Molecular Rotors for Photothermal Combating of Bacterial Biofilms.

The ever-increasing threats of multidrug-resistant bacteria and their biofilm-associated infections have bred a desperate demand for alternative remedies to combat them. Near-infrared (NIR)-absorbing photothermal agent (PTAs)-mediated photothermal therapy (PTT) is particularly attractive for biofilm ablation thanks to its superiorities of noninvasive intervention, satisfactory antibacterial efficiency, and less likelihood to develop resistance. Herein, three butterfly-shaped aggregation-induced emission luminogens (AIEgens) with balanced nonradiative decay (for conducting PTT) and radiative decay (for supplying fluorescence in the NIR-II optical window) are rationally designed for imaging-assisted photothermal obliteration of bacterial biofilms.

Aggregation-Induced Emission-Based Macrophage-Like Nanoparticles for Targeted Photothermal Therapy and Virus Transmission Blockage in Monkeypox.

The recent prevalence of monkeypox has led to the declaration of a Public Health Emergency of International Concern. Monkeypox lesions are typically ulcers or pustules (containing high titers of replication-competent virus) in the skin and mucous membranes, which allow monkeypox virus to transmit predominantly through intimate contact. Currently, effective clinical treatments for monkeypox are lacking, and strategies for blocking virus transmission are fraught with drawbacks.

More Is Better: Dual-Acceptor Engineering for Constructing Second Near-Infrared Aggregation-Induced Emission Luminogens to Boost Multimodal Phototheranostics.

The manipulation of electron donor/acceptor (D/A) shows an endless impetus for innovating optical materials. Currently, there is booming development in electron donor design, while research on electron acceptor engineering has received limited attention. Inspired by the philosophical idea of "more is different", two systems with D'-D-A-D-D' (1A system) and D'-D-A-A-D-D' (2A system) structures based on acceptor engineering were designed and studied.