Red/NIR emissive aggregation-induced emission-active photosensitizers with strong donor-acceptor strength for image-guided photodynamic therapy of cancer.

Light-mediated therapies such as photodynamic therapy (PDT) are considered emerging cancer treatment strategies. However, there are still lots of defect with common photosensitizers (PSs), such as short emission wavelength, weak photostability, poor cell permeability, and low PDT efficiency. Therefore, it is very important to develop high-performance PSs. Recently, luminogens with aggregation-induced emission (AIE) characteristics and red/near-infrared (NIR) emissive have been reported as promising PSs for image-guided cancer therapy, due to them being able to prevent autofluorescence in physiological environments, their enhanced fluorescence in the aggregated state, and generation of reactive oxygen species (ROS). Herein, we developed PSs named TBTCPM and MTBTCPM with donor-acceptor (D-A) structures, strong red/NIR, excellent targeting specificities to good cell permeability, and high photostability. Interestingly, both of them can efficiently generate ROS under white light irradiation and possess excellent killing effect on cancer cells. This study, thus, not only demonstrates applications in cell image-guided PDT cancer therapy performances but also provides strategy for construction of AIEgens with long emission wavelengths.

Precise Molecular Engineering of Type I Photosensitizer with Aggregation-Induced Emission for Image-Guided Photodynamic Eradication of Biofilm.

Biofilm-associated infections exert more severe and harmful attacks on human health since they can accelerate the generation and development of the antibiotic resistance of the embedded bacteria. Anti-biofilm materials and techniques that can eliminate biofilms effectively are in urgent demand. Therefore, we designed a type I photosensitizer (TTTDM) with an aggregation-induced emission (AIE) property and used F-127 to encapsulate the TTTDM into nanoparticles (F-127 AIE NPs). The NPs exhibit highly efficient ROS generation by enhancing intramolecular D-A interaction and confining molecular non-radiative transitions. Furthermore, the NPs can sufficiently penetrate the biofilm matrix and then detect and eliminate mature bacterial biofilms upon white light irradiation. This strategy holds great promise for the rapid detection and eradication of bacterial biofilms.

Recent advances in aggregation-induced emission luminogens in photoacoustic imaging.

Photoacoustic imaging (PAI) is a rapidly emerging modality in biomedical research with the advantages of noncontact operation, high optical resolution, and deep penetration. Great efforts and progress in the development of PAI agents with improved imaging resolution and sensitivity have been made over the past 2 decades. Among them, organic agents are the most promising candidates for preclinical/clinical applications due to their outstanding in vivo properties and facile biofunctionalities. Motivated by the unique properties of aggregation-induced emission (AIE) luminogens (AIEgens), various optical probes have been developed for bioanalyte detection, multimodal bioimaging, photodynamic/photothermal therapy, and imaging-guided therapeutics. In particular, AIE-active contrast agents have been demonstrated in PAI applications with excellent performance in imaging resolution and tissue permeability in vivo. This paper presents a brief overview of recent progress in AIE-based agents in the field of photoacoustic imaging. In particular, we focus on the basic concepts, data sorting and comparison, developing trends, and perspectives of photoacoustic imaging. Through numerous typical examples, the way each system realizes the desired photoacoustic performance in various biomedical applications is clearly illustrated. We believe that AIE-based PAI agents would be promising multifunctional theranostic platforms in clinical fields and will facilitate significant advancements in this research topic.

Tunable Linear and Nonlinear Optical Properties from Room Temperature Phosphorescent Cyclic Triimidazole-Pyrene Bio-Probe.

Organic materials with multiple emissions tunable by external stimuli represent a great challenge. TTPyr, crystallizing in different polymorphs, shows a very rich photophyisics comprising excitation-dependent fluorescence and phosphorescence at ambient conditions, and mechanochromic and thermochromic behavior. Transformation among the different species has been followed by thermal and X-ray diffraction analyses and the emissive features interpreted through structural results and DFT/TDDFT calculations. Particularly intriguing is the polymorph TTPyr(HT), serendipitously obtained at high temperature but stable also at room temperature, whose non-centrosymmetric structure guarantees an SHG efficiency 10 times higher than that of standard urea. Its crystal packing, where only the TT units are strongly rigidified by π-π stacking interactions while the Pyr moieties possess partial conformational freedom, is responsible for the observed dual fluorescence. The potentialities of TTPyr for bioimaging have been successfully established.

Aptamer-Decorated Self-Assembled Aggregation-Induced Emission Organic Dots for Cancer Cell Targeting and Imaging.

A facile and simple one-step method was developed to fabricate aptamer-decorated self-assembled organic dots with aggregation-induced emission (AIE) characteristics. With integration of the advantages of AIE aggregates with strong emission and the cell-targeting capability of aptamers, the as-prepared Apt-AIE organic nanodots can specifically target to cancer cells with good biocompatibility, high image constrast, and photostability. On the basis of this universal method, a variety of versatile organic fluorescent nanoprobes with high brightness, specific recognition, and clinical-transitional potential could be facilely constructed for biological sensing and imaging applications.

Study of transient absorption spectroscopy of a D-π-A structure aggregation-induced emission luminogen and its photodynamic therapy application.

Photodynamic therapy (PDT) represents an emerging and noninvasive modality that has gained clinical approval for the treatment of cancers, leveraging photosensitizers for optimal therapeutic efficacy. In this study, we synthesized a photosensitizer (denoted as DTCSPP) exhibiting a donor-π-acceptor (D-π-A) structural motif. The DTCSPP manifests aggregation-induced emission (AIE) characteristics, along with good biocompatibility and mitochondrial targeting capabilities attributed to its intrinsic charge and D-π-A architecture. The excited-state intramolecular charge transfer of DTCSPP was systematically investigated in both solution and aggregate states using femtosecond transient absorption spectroscopy (fs-TA). The fs-TA results revealed that DTCSPP exhibited a more rapid and facile excited-state molecular motion in the solution state compared to the aggregate state, implying the predominance of nonradiative decay in its photophysical processes within the solution. Given its ability to simultaneously generate type I and type II reactive oxygen species and induce ferroptosis and autophagy in cancer cells, DTCSPP demonstrates effectiveness in PDT at both cellular and in vivo levels. This study contributes a comprehensive understanding of the excited-state intramolecular charge transfer dynamics of charged D-π-A type AIE photosensitizers, shedding light on their potential application in PDT. The multifaceted capabilities of DTCSPP underscore its promise in advancing the field of anticancer therapeutics, providing valuable insights for the identification of anticancer targets and the development of novel drugs.

A photostable AIE luminogen for specific mitochondrial imaging and tracking.

Tracking the dynamics of mitochondrial morphology has attracted much research interest because of its involvement in early stage apoptosis and degenerative conditions. To follow this process, highly specific and photostable fluorescent probes are in demand. Commercially available mitochondria trackers, however, suffer from poor photostability. To overcome this limitation, we have designed and synthesized a fluorescent agent, tetraphenylethene-triphenylphosphonium (TPE-TPP), for mitochondrial imaging. Inherent from the mitochondrial-targeting ability of TPP groups and the aggregation-induced emission (AIE) characteristics of the TPE core, TPE-TPP possesses high specificity to mitochondria, superior photostability, and appreciable tolerance to environmental change, allowing imaging and tracking of the mitochondrial morphological changes in a long period of time.

A type I AIE photosensitiser-loaded biomimetic nanosystem allowing precise depletion of cancer stem cells and prevention of cancer recurrence after radiotherapy.

Radioresistance of Cancer stem cell (CSC) is an important cause of tumor recurrence after radiotherapy (RT). Herein, we designed a type I aggregation-induced emission (AIE) photosensitiser-loaded biomimetic mesoporous organosilicon nanosystem (PMT) for precise depletion of CSC to prevent tumor recurrence after RT. This PMT system is composed of a type I AIE photosensitiser (TBP-2) loaded mesoporous organosilicon nanoparticles (MON) with an outer platelet membrane. The PMT system is able to specifically target CSC. Intracellular glutathione activity leads to MON degradation and the release of TBP-2. Type I photodynamic therapy is activated by exposure to white light, producing a large amount of hydroxyl radicals to promote CSC death. The results of in vivo experiments demonstrated specific removal of CSC following PMT treatment, with no tumor recurrence observed when combined with RT. However, tumor recurrence was observed in mice that received RT only. The expression of CSC markers was significantly reduced following PMT treatment. We demonstrate the development of a system for the precise removal of CSC with good biosafety and high potential for clinical translation. We believe the PMT nanosystem represents a novel idea in the prevention of tumor recurrence.

Photothermal-Triggered Sulfur Oxide Gas Therapy Augments Type I Photodynamic Therapy for Potentiating Cancer Stem Cell Ablation and Inhibiting Radioresistant Tumor Recurrence.

Despite advances in cancer therapy, the existence of self-renewing cancer stem cells (CSC) can lead to tumor recurrence and radiation resistance, resulting in treatment failure and high mortality in patients. To address this issue, a near-infrared (NIR) laser-induced synergistic therapeutic platform has been developed by incorporating aggregation-induced emission (AIE)-active phototheranostic agents and sulfur dioxide (SO2 ) prodrug into a biocompatible hydrogel, namely TBH, to suppress malignant CSC growth. Outstanding hydroxyl radical (·OH) generation and photothermal effect of the AIE phototheranostic agent actualizes Type I photodynamic therapy (PDT) and photothermal therapy through 660 nm NIR laser irradiation. Meanwhile, a large amount of SO2 is released from the SO2 prodrug in thermo-sensitive TBH gel, which depletes upregulated glutathione in CSC and consequentially promotes ·OH generation for PDT enhancement. Thus, the resulting TBH hydrogel can diminish CSC under 660 nm laser irradiation and finally restrain tumor recurrence after radiotherapy (RT). In comparison, the tumor in the mice that were only treated with RT relapsed rapidly. These findings reveal a double-boosting ·OH generation protocol, and the synergistic combination of AIE-mediated PDT and gas therapy provides a novel strategy for inhibiting CSC growth and cancer recurrence after RT, which presents great potential for clinical treatment.

Monitoring and inhibition of insulin fibrillation by a small organic fluorogen with aggregation-induced emission characteristics.

Amyloid fibrillation of proteins is associated with a great variety of pathologic conditions. Development of new molecules that can monitor amyloidosis kinetics and inhibit fibril formation is of great diagnostic and therapeutic value. In this work, we have developed a biocompatible molecule that functions as an ex situ monitor and an in situ inhibitor for protein fibrillation, using insulin as a model protein. 1,2-Bis[4-(3-sulfonatopropoxyl)phenyl]-1,2-diphenylethene salt (BSPOTPE) is nonemissive when it is dissolved with native insulin in an incubation buffer but starts to fluoresce when it is mixed with preformed insulin fibril, enabling ex situ monitoring of amyloidogenesis kinetics and high-contrast fluorescence imaging of protein fibrils. Premixing BSPOTPE with insulin, on the other hand, inhibits the nucleation process and impedes the protofibril formation. Increasing the dose of BSPOTPE boosts its inhibitory potency. Theoretical modeling using molecular dynamics simulations and docking reveals that BSPOTPE is prone to binding to partially unfolded insulin through hydrophobic interaction of the phenyl rings of BSPOTPE with the exposed hydrophobic residues of insulin. Such binding is assumed to have stabilized the partially unfolded insulin and obstructed the formation of the critical oligomeric species in the protein fibrillogenesis process.

On-surface synthesis and spontaneous segregation of conjugated tetraphenylethylene macrocycles.

Creating conjugated macrocycles has attracted extensive research interest because their unique chemical and physical properties, such as conformational flexibility, intrinsic inner cavities and aromaticity/antiaromaticity, make these systems appealing building blocks for functional supramolecular materials. Here, we report the synthesis of four-, six- and eight-membered tetraphenylethylene (TPE)-based macrocycles on Ag(111) via on-surface Ullmann coupling reactions. The as-synthesized macrocycles are spontaneously segregated on the surface and self-assemble as large-area two-dimensional mono-component supramolecular crystals, as characterized by scanning tunneling microscopy (STM). We propose that the synthesis benefits from the conformational flexibility of the TPE backbone in distinctive multi-step reaction pathways. This study opens up opportunities for exploring the photophysical properties of TPE-based macrocycles.

Quantitation, visualization, and monitoring of conformational transitions of human serum albumin by a tetraphenylethene derivative with aggregation-induced emission characteristics.

Human serum albumin (HSA) is a major protein component of blood plasma, and its assay is of obvious value to biological research. We, herein, present a readily accessible fluorescent bioprobe for HSA detection and quantitation. A nonemissive tetraphenylethene derivative named sodium 1,2-bis[4-(3-sulfonatopropoxyl)phenyl]-1,2-diphenylethene (BSPOTPE) is induced to emit by HSA, showing a novel phenomenon of aggregation-induced emission (AIE). The AIE bioprobe enjoys a broad working range (0-100 nM), a low detection limit (down to 1 nM), and a superior selectivity to albumins. The fluorescent bioassay is unperturbed by the miscellaneous bioelectrolytes in the artificial urine. The AIE luminogen can also be used as a rapid and sensitive protein stain in gel electrophoresis for HSA visualization. Utilizing the AIE feature of BSPOTPE and the Forster resonance energy transfer from HSA to BSPOTPE, the unfolding process of HSA induced by guanidine hydrochloride is monitored, which reveals a multistep transition with the involvement of molten globule intermediates. Computational modeling suggests that the AIE luminogens dock in the hydrophobic cleft between subdomains IIA and IIIA of HSA with the aid of hydrophobic effect, charge neutralization, and hydrogen bonding interactions, offering mechanistic insight into the microenvironment inside the hydrophobic cavity.

Fluorescent bioprobes: structural matching in the docking processes of aggregation-induced emission fluorogens on DNA surfaces.

Whereas most conventional DNA probes are flat disklike aromatic molecules, we explored the possibility of developing quadruplex sensors with nonplanar conformations, in particular, the propeller-shaped tetraphenylethene (TPE) salts with aggregation-induced emission (AIE) characteristics. 1,1,2,2-Tetrakis[4-(2-triethylammonioethoxy)phenyl]ethene tetrabromide (TPE-1) was found to show a specific affinity to a particular quadruplex structure formed by a human telomeric DNA strand in the presence of K(+) ions, as indicated by the enhanced and bathochromically shifted emission of the AIE fluorogen. Steady-state and time-resolved spectral analyses revealed that the specific binding stems from a structural matching between the AIE fluorogen and the DNA strand in the folding process. Computational modeling suggests that the AIE molecule docks on the grooves of the quadruplex surface with the aid of electrostatic attraction. The binding preference of TPE-1 enables it to serve as a bioprobe for direct monitoring of cation-driven conformational transitions between the quadruplexes of various conformations, a job unachievable by the traditional G-quadruplex biosensors. Methyl thiazolyl tetrazolium (MTT) assays reveal that TPE-1 is cytocompatible, posing no toxicity to living cells.

Chiral poly(4-ethynylbenzoyl-l-valine)-induced helical self-assembly of alkynylplatinum(II) terpyridyl complexes with tunable electronic absorption, emission, and circular dichroism changes.

A chiral amino acid-containing polyacetylene, poly(4-ethynylbenzoyl-L-valine), was found to induce the aggregation and self-assembly of square-planar alkynylplatinum(II) terpyridyl complexes by electrostatic binding of the positively charged metal complexes to the anionic sites of the polyacetylene, as revealed by the appearance of new UV/Vis absorption and emission bands upon mixing under basic conditions. The induced complex self-assembly was found to be influenced by the polyacetylene and/or base concentration, and the effect of pH on the reversibility of the aggregate/monomer interconversion was also studied. The conformational changes of the polyacetylene were probed by circular dichroism (CD) spectroscopy, in which the chirality signal of the corresponding chain helicity in the presence of the base was enhanced and stabilized upon addition of the platinum(II) complexes. The induced complex aggregation was dependent on the structural properties of the polyacetylene, while the chirality of the polyacetylene was strongly influenced by the introduction of the complex.

AIE-based theranostic systems for detection and killing of pathogens.

Pathogenic bacteria, fungi and viruses pose serious threats to the human health under appropriate conditions. There are many rapid and sensitive approaches have been developed for identification and quantification of specific pathogens, but many challenges still exist. Culture/colony counting and polymerase chain reaction are the classical methods used for pathogen detection, but their operations are time-consuming and laborious. On the other hand, the emergence and rapid spread of multidrug-resistant pathogens is another global threat. It is thus of utmost urgency to develop new therapeutic agents or strategies. Luminogens with aggregation-induced emission (AIEgens) and their derived supramolecular systems with unique optical properties have been developed as fluorescent probes for turn-on sensing of pathogens with high sensitivity and specificity. In addition, AIE-based supramolecular nanostructures exhibit excellent photodynamic inactivation (PDI) activity in aggregate, offering great potential for not only light-up diagnosis of pathogen, but also image-guided PDI therapy for pathogenic infection.

Bio-orthogonal AIE Dots Based on Polyyne-Bridged Red-emissive AIEgen for Tumor Metabolic Labeling and Targeted Imaging.

In this work, we aim to develop cancer cell-targeting AIE dots based on a polyyne-bridged red-emissive AIEgen, 2TPE-4E, through the combination of metabolic engineering and bio-orthogonal reactions. Azide groups on a tumor were efficiently produced by intravenous injection of Ac4ManNAz and glycol-metabolic engineering. These bio-orthogonal azide groups could facilitate the specific targeting of DBCO-AIE dots to the tumor cells undergoing metal-free click reaction in vivo. The efficiency of this targeting strategy could be further improved with the development of new bio-orthogonal chemical groups with higher reactivity and a large amount of AIEgens could be delivered to the tumor for diagnosis.

Theranostics based on AIEgens.

The utilization of luminogens with aggregation-induced emission (AIE) characteristics has recently been developed at a tremendous pace in the area of theranostics, mainly because AIE luminogens (AIEgens) hold various distinct advantages, such as good biocompatibility, excellent fluorescence properties, simple preparation and modification, perfect size of nano-aggregation for enhanced permeability and retention effect, promoted efficiencies of photodynamic and photothermal therapies, efficient photoacoustic imaging, and ready constructions of multimodal imaging and therapy. Significant breakthroughs and developments of theranostics based on AIEgens have been achieved in the past few years, and great progress has been witnessed in many theranostic modalities, indicating that AIEgens remarkably complement conventional theranostic materials and promote the development of theranostics. This review provides theoretical insights into the advantages of AIEgens in theranostics, and systematically summarizes the basic concepts, seminal studies, recent trends and perspectives in theranostics based on AIEgens. We believe that AIEgens would be promising multifunctional theranostic platforms in clinical fields and facilitate significant advancements in this research-active area.

Metallized hyperbranched polydiyne: a photonic material with a large refractive index tunability and a spin-coatable catalyst for facile fabrication of carbon nanotubes.

A cobalt-containing hyperbranched polydiyne shows refractive indexes (n) as high as 1.713-1.813 in the long wavelength region, which can be tuned to a large extent (Deltan up to approximately 0.048) by UV irradiation; the polymer can also function as a spin-coatable catalyst for the growth of carbon nanotubes.

A Lysosome-Targeting AIEgen for Autophagy Visualization.

In this work, a morpholine-functionalized aggregation-induced emission luminogen (AIEgen), AIE-LysoY, is reported for lysosomal imaging and autophagy visualization. To attain outstanding imaging contrast, AIE-LysoY is equipped with excited state intramolecular proton transfer (ESIPT) characteristic. AIE-LysoY provides a new platform for lysosome visualization with good biocompatibility, large Stokes shift, superior signal-to-noise ratio, and high photostability.

Self-assembled film of poly(4-carboxyphenyl)acetylene and diazoresin and its photoelectric conversion property.

A novel multilayer film was assembled from water-soluble poly(4-carboxyphenyl)acetylene sodium salt (PCPA) and diazoresin (DR) in aqueous solution via electrostatic attraction. Under UV irradiation, following the decomposition of the diazonium group between the adjacent interfaces of the multilayers, the ionic bonds of the self-assembled film convert to covalent bonds and the film becomes very stable toward electrolyte aqueous solutions. Thus, the photoelectric conversion property of PCPA-containing film can be measured in a conventional three-electrode photoelectrochemical cell, and 0.5 mol/l KCl solution can be used as the supporting electrolyte. The photocurrent spectroscopy response coincides with the absorption spectrum of the irradiated self-assembled film, which indicates that the irradiated DR/PCPA film is responsible for the photocurrent generation.