Complex-mediated nucleophilic aromatic substitution with aryl nitriles to realize intramolecular flapping-restricted D-A AIEgens for bioimaging.

Donor-acceptor (D-A) compounds are particularly important in optoelectronic and biological applications. However, they are normally synthesized in the presence of transition metal catalysts. Herein, we report a metal-free method by a complex-mediated nucleophilic aromatic substitution of aryl nitriles with amines.

Regioisomeric Engineering of Sterically Hindered Bright Near-Infrared Paraptosis Agents for Chemo-Photodynamic Therapy.

Paraptosis emerges as a new promising form of programmed nonapoptotic cell death in chemotherapeutic anticancer therapy. However, current paraptosis agents face critical challenges, including poor targeting specificity, limited imaging capability, and low therapeutic efficacy. To overcome these limitations, we developed a novel approach by functionalizing the tetraphenylethylene (TPE) unit at the position of xanthene dyes, enabling the synthesis of two sterically hindered regioisomeric fluorescent paraptosis-inducing agents (-TSX and -TSX) for mitochondria-targeted chemo-photodynamic anticancer therapy.

Reaction-free mitochondrial membrane potential independent luminogens with aggregation-induced emission characteristics for live neuron imaging.

We developed novel photostable mitochondria targeting probes based on aggregation-induced emission (AIE) luminogens with a cyanostilbene core. The introduction of an alkyl chain onto the pyridinium moiety enhanced their interaction with the mitochondrial membrane. This design effectively prevents probe leakage following mitochondrial membrane depolarization while significantly reducing cytotoxicity.

Harnessing Cross-strand π-π Interlocking for Synergistic Enhancement of Immune Checkpoint Blocking and Ferroptosis.

The dynamic nature of noncovalent bonds in peptide self-assembly allows for selective accommodation of guest molecules. However, it remains unclear how to harness coassembly to reinforce the host peptides and simultaneously improve the application defects of guest molecules. This study aims to achieve supramolecular synergy between the host and guest, further expanding the functional space of the hybrid nanostructures.

π-π Stacking Network-Based Supramolecular Peptide Nanoprobe for Visualization of the ICB-Enhanced Ferroptosis Process.

The construction of coassembled peptide nanoprobes based on structural adaptation provides an effective template for stable monitoring of the molecular events in physiological and pathological processes. This also greatly expands their applications in biomedicine, such as multimodal combined diagnosis and treatment. However, the insufficient understanding of the physicochemical properties and structural features of different molecules still makes it difficult to construct the coassembled probes with mutually reinforcing functions, leading to unpredictable effects.

Recent Advances in Fluorescent Probes for Cancer Biomarker Detection.

Many important biological species have been identified as cancer biomarkers and are gradually becoming reliable targets for early diagnosis and late therapeutic evaluation of cancer. However, accurate quantitative detection of cancer biomarkers remains challenging due to the complexity of biological systems and the diversity of cancer development. Fluorescent probes have been extensively utilized for identifying biological substances due to their notable benefits of being non-invasive, quickly responsive, highly sensitive and selective, allowing real-time visualization, and easily modifiable.

A novel ratiometric fluorescent probe with high selectivity for lysosomal nitric oxide imaging.

Nitric oxide (NO) plays critical roles in both physiology and pathology, serving as a significant signaling molecule. Recent investigations have uncovered the pivotal role of lysosome as a critical organelle where intracellular NO exists and takes function. In this study, we developed a novel ratiometric fluorescent probe called XL-NO and modified it with a morpholine unit, which followed the intramolecular charge transfer (ICT) mechanism.

Effects of Halogenation on Quinoline-Malononitrile-based AIEgens: Photophysical Properties Investigation and Wash-Free Imaging.

Developing halogen-functionalized fluorescent dyes with intriguing photophysical properties, including enhanced photostability, is particularly important for bioimaging. In this work, we synthesized two new halogen-functionalized aggregation-induced emission (AIE)-active molecules, DQMF-OH and DQMCl-OH, based on the quinoline-malononitrile chromophore. The halogen effect on the photophysical characteristics was detailedly studied by absorption and fluorescence spectroscopy, density functional theory calculations, and crystal structures.

Aggregation-Enhanced Photophysical Performance of D-π-A Structured Hemicyanine for NIR-II Fluorescent and Photoacoustic Imaging-Guided Photothermal Therapy.

Near-infrared (NIR)-II fluorescence and photoacoustic (PA) dual-model imaging-guided photothermal therapy (PTT) can precisely diagnose and treat tumors and evaluate the therapeutic efficacy in real-time. Herein, we utilized a donor-π-acceptor (D-π-A) structured hemicyanine dye (named M1) with a large conjugated structure and strong intramolecular charge transfer effect and demonstrated that the aggregation of M1 could significantly enhance its photophysical performance by improving its photostability and photothermal conversion capability as compared with M1 in a single molecular state. Furthermore, we prepared water-dispersible NIR-II fluorescent nanoparticles (M1 NPs) by wrapping M1 with DSPE-PEG2000-NH.

Donor-Acceptor-Acceptor-Conjugated Dual-State Emissive Acrylonitriles: Investigating the Effect of Acceptor Unit Order and Biological Imaging.

The effect of acceptor unit order on the photophysical properties of two distinct donor-acceptor-acceptor conjugated fluorescent acrylonitriles, TPA-AN-PhBT and TPA-BT-ANPh, was systematically investigated. Compared with faintly emissive TPA-AN-PhBT in solution, TPA-BT-ANPh showed strong red-shifted fluorescence. TPA-AN-PhBT and TPA-BT-ANPh exhibited enhanced green and deep red emissions with remarkable fluorescence quantum yields up to 44% in the solid state.

One-Pot Synthesis of Pyreno[2,1-b]furan Molecules with Two-Photon Absorption Properties.

The development of large π-conjugated polycyclic heteroaromatic materials is of immense interest, both in the academic as well as the industrial community. Herein, we present the efficient one-pot synthesis of novel pyreno[2,1-b]furan molecules from a newly designed intermediate, which display intense green emission (505-516 nm) in solution and a large red shift emission (625-640 nm) in the solid state, because of strong π-π stacking. More interestingly, the compounds exhibit novel two-photon absorption (TPA) properties, and the TPA cross-section (δ) value was increased to 533 GM by regulating the electronic effects of the substituents of the pyreno[2,1-b]furan molecules.

Structure Rigidification Promoted Ultrabright Solvatochromic Fluorescent Probes for Super-Resolution Imaging of Cytosolic and Nuclear Lipid Droplets.

Lipid droplets (LDs) containing cytosolic and nuclear LDs have recently received increasing attention because of their diverse biological roles in living systems. However, developing fluorescent probes for super-resolution visualization of these subcellular LDs still remains challenging due to insufficient fluorescence brightness and poor nuclear membrane permeability. Herein, we rationally synthesized a series of ultrabright solvatochromic fluorescent probes based on benzoboranils (BBAs) for LD-specific super-resolution imaging using structured illumination microscopy (SIM).

Precise and long-term tracking of mitochondria in neurons using a bioconjugatable and photostable AIE luminogen.

Tracking mitochondrial movement in neurons is an attractive but challenging research field as dysregulation of mitochondrial motion is associated with multiple neurological diseases. To realize accurate and long-term tracking of mitochondria in neurons, we elaborately designed a novel aggregation-induced emission (AIE)-active luminogen, TPAP-C5-yne, where we selected a cationic pyridinium moiety to target mitochondria and employed an activated alkyne terminus to achieve long-term tracking through bioconjugation with amines on mitochondria. For the first time, we successfully achieved the accurate analysis of the motion of a single mitochondrion in live primary hippocampal neurons and the long-term tracking of mitochondria for up to a week in live neurons.

Exploiting the Twisted Intramolecular Charge Transfer Effect to Construct a Wash-Free Solvatochromic Fluorescent Lipid Droplet Probe for Fatty Liver Disease Diagnosis.

The prominent pathological feature of fatty liver disease lesions is excessive fat accumulation in lipid droplets in hepatocytes. Thus, developing fluorescent lipid droplet-specific probes with high permeability and a high imaging contrast provides a robust tool for diagnosing fatty liver diseases. Herein, we rationally developed a novel donor-acceptor lipophilic fluorescent probe ANI with high photostability for wash-free visualization of lipid droplets and fatty liver disease characteristics.

Near-Infrared Light-Triggered Lysosome-Targetable Carbon Dots for Photothermal Therapy of Cancer.

Photothermal therapy (PTT) has inherent advantages in the treatment of hypoxic tumors due to its optically controlled selectivity on tumor ablation and oxygen-independent nature. The subcellular organelle-targeting capability and photothermal conversion efficiency (PCE) at near-infrared (NIR) wavelength are the key parameters in the assessment of the photothermal agent (PTA). Here, we report that carbon dots (CDs) prepared by the hydrothermal treatment of coronene derivatives show a high PCE of 54.

A pH-Sensitive Spirocyclization Strategy for Constructing a Single Fluorescent Probe Simultaneous Two-Color Visualizing of Lipid Droplets and Lysosomes and Monitoring of Lipophagy.

Lipid droplets (LDs) and lysosomes are crucial for maintaining intracellular homeostasis. But single fluorescent probes (SFPs) capable of simultaneous and discriminative visualizing of two organelles above and their interaction in living cells are still challenging due to the lack of rational design strategies. To break this bottleneck, herein, we develop a reliable strategy based on a pH-sensitive intramolecular spirocyclization.

Two-Color Visualization of Cholesterol Fluctuation in Plasma Membranes by Spatial Distribution-Controllable Single Fluorescent Probes.

Visualizing cholesterol (CL) fluctuation in plasma membranes is a crucially important yet challenging task in cell biology. Here, we proposed a new imaging strategy based on permeability changes of plasma membranes triggered by different CL contents to result in controllable spatial distribution of single fluorescent probes (SF-probes) in subcellular organelles. Three spatial distribution-controllable SF-probes (PMM-Me, PMM-Et, and PMM-Bu) for imaging CL fluctuation in plasma membranes were rationally developed.

Simultaneous Two-Color Visualization of Lipid Droplets and Endoplasmic Reticulum and Their Interplay by Single Fluorescent Probes in Lambda Mode.

In living systems, subcellular organelles mutually cooperate and closely contact to form organelle interaction networks. Thus, the simultaneous and discriminative visualization of different organelles is extremely valuable for elucidating their distribution and interplay. However, such meaningful investigations remain a great challenge due to the lack of advanced single fluorescent probes (SF-probes) capable of simultaneous and two-color imaging of two targets.

A Single Fluorescent pH Probe for Simultaneous Two-Color Visualization of Nuclei and Mitochondria and Monitoring Cell Apoptosis.

Subcellular organelles play indispensable roles in diverse biological processes by their precise mutual cooperation. Thus, the development of a single fluorescent probe (SF-probe) for simultaneous and discriminable visualization of different organelles and their dynamics during certain bioprocess is significant, yet remains greatly challenging. Herein, for the first time, we rationally prepared a pH-sensitive SF-probe (named HMBI) for the simultaneous two-color visualization of nuclei and mitochondria and monitoring cell apoptosis.

Fluorescent AIE-Active Materials for Two-Photon Bioimaging Applications.

Fluorescence imaging has been widely used as a powerful tool for and real-time visualization of important analytes and biological events in live samples with remarkably high selectivity, sensitivity, and spatial resolution. Compared with one-photon fluorescence imaging, two-photon fluorescence imaging exhibits predominant advantages of minimal photodamage to samples, deep tissue penetration, and outstanding resolution. Recently, the aggregation-induced emission (AIE) materials have become a preferred choice in two-photon fluorescence biological imaging because of its unique bright fluorescence in solid and aggregate states and strong resistance to photobleaching.

Fabrication of small-structure red-emissive fluorescent probes for plasma membrane enables quantification of nuclear to cytoplasmic ratio in live cells and tissues.

Nuclear to cytoplasmic ratio is one of the vital parameters in diagnosis of cancer by means of hematoxylin-eosin (HE) stained histopathology. However, HE histopathology dependent on mechanical tissue slice damages biosamples and exhibits insufficient accuracy. Herein, we rationally prepared two small-molecule plasma membrane fluorescent probes with red-emitting fluorescence for visualizing plasma membrane in living cells and tissues.

Bright Aggregation-Induced Emission Nanoparticles for Two-Photon Imaging and Localized Compound Therapy of Cancers.

Photodynamic therapy (PDT), a noninvasive therapeutic strategy for cancer treatment, which always suffers from the low reactive oxygen species (ROS) yield of traditional organic dyes. Herein, we present lipid-encapsulated aggregation-induced emission nanoparticles (AIE NPs) that have a high quantum yield (23%) and a maximum two-photon absorption (TPA) cross-section of 560 GM irradiated by near-infrared light (800 nm). The AIE NPs can serve as imaging agents for spatiotemporal imaging of tumor tissues with a penetration depth up to 505 μm on mice melanoma model.

Highly Efficient Aggregation-Induced Red-Emissive Organic Thermally Activated Delayed Fluorescence Materials with Prolonged Fluorescence Lifetime for Time-Resolved Luminescence Bioimaging.

Organic thermally activated delayed fluorescence (TADF) materials are emerging as potential candidates for time-resolved fluorescence imaging in biological systems. However, the development of purely organic TADF materials with bright aggregated-state emissions in the red/near-infrared (NIR) region remains challenging. Here, we report three donor-acceptor-type TADF molecules as promising candidates for time-resolved fluorescence imaging, which are engineered by direct connection of electron-donating moieties (phenoxazine or phenothiazine) and an electron-acceptor 1,8-naphthalimide (NI).