Recent advances of AIE light-up probes for photodynamic therapy

As a new non-invasive treatment method, photodynamic therapy (PDT) has attracted great attention in biomedical applications. The advantages of possessing fluorescence for photosensitizers have made it possible to combine imaging and diagnosis together with PDT. The unique features of aggregation-induced emission (AIE) fluorogens provide new opportunities for facile design of light-up probes with high signal-to-noise ratios and improved theranostic accuracy and efficacy for image-guided PDT. In this review, we summarize the recent advances of AIE light-up probes for PDT. The strategies and principles to design AIE photosensitizers and light-up probes are firstly introduced. The application of AIE light-up probes in photodynamic antitumor and antibacterial applications is further elaborated in detail, from binding/targeting-mediated, reaction-mediated, and external stimuli-mediated light-up aspects. The challenges and future perspectives of AIE light-up probes in the PDT field are also presented with the hope to encourage more promising developments of AIE materials for phototheranostic applications and translational research.

AIE fluorogens provide new opportunities for the development of light-up probes for photodynamic therapy.     

Fluorescent polymer cubosomes and hexosomes with aggregation-induced emission

Fluorescent polymer cubosomes and hexosomes with aggregation-induced emission (AIE) were prepared from amphiphilic block copolymers PEG-b-PTPEMA where the hydrophobic block PTPEMA was a polymethacrylate with tetraphenylethene (TPE) as the AIE side group. Four highly asymmetric block copolymers with hydrophilic block weight ratio f_PEG ≤ 20% were synthesized. Cubosomes and hexosomes with strong fluorescence emission were obtained by nanoprecipitation of polymers with f_PEG < 9% in dioxane/water and THF/water systems. Their ordered internal structures were studied by electron microscopy (cryo-EM, SEM and TEM) and the X-ray scattering technique (SAXS). To elucidate the formation mechanisms of these inverted colloids, other parameters influencing the morphologies, like the water content during self-assembly and the organic solvent composition, were also investigated. This study not only inspires people to design novel building blocks for the preparation of functional cubosomes and hexosomes, but also presents the first AIE fluorescent polymer cubosome and hexosome with potential applications in bio-related fields.

Fluorescent Im$\bar{3}$m cubosome and P6mm hexosome with aggregation-induced emission (AIE) were reported, which were formed by amphiphilic block copolymers PEG-b-PTPEMA. The length of hydrophobic block PTPEMA was adjusted to control morphology formation.     

AIE-based nanoaggregate tracker: high-fidelity visualization of lysosomal movement and drug-escaping processes

High-fidelity imaging and long-term visualization of lysosomes are crucial for their functional evaluation, related disease detection and active drug screening. However, commercial aggregation-caused quenching probes are not conducive to precise lysosomal imaging because of their inherent drawbacks, like easy diffusion, short emission and small Stokes shift, let alone their long-term tracing due to rapid photobleaching. Herein we report a novel aggregation-induced emission (AIE)-based TCM-PI nanoaggregate tracker for direct visualization of lysosomes based on the building block of tricyano-methylene-pyridine (TCM), wherein introduced piperazine (PI) groups behave as targeting units to lysosomes upon protonation, and the self-assembled nanostructure contributes to fast endocytosis for enhanced targeting ability as well as extended retention time for long-term imaging. The piperazine-stabilized TCM-PI nanoaggregate shifts the emission maximum to 677 nm in an aqueous environment, and falls within the desirable NIR region with a large Stokes shift of 162 nm, thereby greatly reducing biological fluorescent background interference. In contrast with the commercially available LysoTracker Red, the essential AIE characteristic of high photostability can guarantee three-dimensional high-fidelity tracing with low photobleaching, and little diffusion from lysosomes, and especially overcome the AIE bottleneck to target specificity. Consequently, the AIE-based nanoaggregate tracker successfully achieves the high-fidelity and long-term tracing of lysosomal movement and even monitors the drug-escaping process from lysosomes to cell nuclei, which provides a potential tool to benefit drug screening.

Well-formed AIE nanoaggregates with good stability can achieve high-fidelity visualization of lysosomal movement and drug-escaping processes.     

Synthesis of an AIEgen functionalized cucurbit[7]uril for subcellular bioimaging and synergistic photodynamic therapy and supramolecular chemotherapy

Aggregation-induced emission (AIE) based fluorophores (AIEgens) have attracted increasing attention for biomedical applications due to their unique optical properties. Here we report an AIE photosensitizer functionalized CB[7], namely AIECB[7], which could spontaneously self-assemble into nanoaggregates in aqueous solutions. Interestingly, the carbonyl-lace of CB[7] may potentially act as a proton acceptor in an acidic environment to fine-tune the fluorescence and singlet oxygen generation of AIECB[7] nanoaggregates by regulating the inner stacking of AIEgens. Additionally, benefiting from the guest-binding properties of CB[7], oxaliplatin was included into AIECB[7] nanoaggregates for combined photodynamic therapy and supramolecular chemotherapy. To show the modular versatility of this supramolecular system, a hypoxia-activatable prodrug banoxantrone (AQ4N) was loaded into AIECB[7] nanoaggregates, which exhibited synergistic antitumor effects on a multicellular tumor spheroid model (MCTS). This work not only provides AIECB[7] for versatile theranostic applications, but also offers important new insights into the design and development of macrocycle-conjugated AIE materials for diverse biomedical applications.

An AIEgen-functionalized cucurbit[7]uril was synthesized for the first time and spontaneously self-assembled into nanoaggregates in aqueous solutions and allowed subcellular imaging of the lysosome and photodynamic therapy and chemotherapy of cancer.     

Quantifying internal charge transfer and mixed ion-electron transfer in conjugated radical polymers

Macromolecular radicals are receiving growing interest as functional materials in energy storage devices and in electronics. With the need for enhanced conductivity, researchers have turned to macromolecular radicals bearing conjugated backbones, but results thus far have yielded conjugated radical polymers that are inferior in comparison to their non-conjugated partners. The emerging explanation is that the radical unit and the conjugated backbone (both being redox active) transfer electrons between each other, essentially “quenching” conductivity or capacity. Here, the internal charge transfer process is quantified using a polythiophene loaded with 0, 25, or 100% nitroxide radicals (2,2,6,6-tetramethyl-1-piperidinyloxy [TEMPO]). Importantly, deconvolution of the cyclic voltammograms shows mixed faradaic and non-faradaic contributions that contribute to the internal charge transfer process. Further, mixed ion-electron transfer is determined for the 100% TEMPO-loaded conjugated radical polymer, from which it is estimated that one triflate anion and one propylene carbone molecule are exchanged for every electron. Although these findings indicate the reason behind their poor conductivity and capacity, they point to how these materials might be used as voltage regulators in the future.

Conjugated radical polymers can exhibit internal electron transfer depending on the radical loading.     

Tuning molecular aggregation to achieve highly bright AIE dots for NIR-II fluorescence imaging and NIR-I photoacoustic imaging

Currently, bright aggregation-induced emission luminogens (AIEgens) with high photoluminescence quantum yields (PLQYs) in the NIR-II region are still limited, and thus an efficient strategy to enhance NIR-II fluorescence performance through tuning molecular aggregation is proposed here. The synthesized donor–acceptor tailored AIEgen (DTPA-TBZ) not only exhibits an excellent absorptivity in the NIR-I region, but also good fluorescence signals in the NIR-II region with an emission extending to 1200 nm. Benefiting from such improved intramolecular restriction and aggregation, a significant absolute PLQY value of 8.98% was obtained in solid DTPA-TBZ. Encouragingly, the resulting AIE dots also exhibit a high relative PLQY of up to 11.1% with IR 26 as the reference (PLQY = 0.5%). Finally, the AIE dots were applied in high performance NIR-II fluorescence imaging and NIR-I photoacoustic (PA) imaging: visualization of abdominal vessels, hind limb vasculature, and cerebral vessels with high signal to background ratios was performed via NIR-II imaging; Moreover, PA imaging has also been performed to clearly observe tumors in vivo. These results demonstrate that by finely tuning molecular aggregation in DTPA-TBZ, a good NIR-I absorptivity and a highly emissive fluorescence in the NIR-II region can be achieved simultaneously, finally resulting in a promising dual-modal imaging platform for real-world applications to achieve precise cancer diagnostics.

A highly efficient dual-modal imaging platform by using bright AIE dots was constructed to achieve precise cancer diagnostics.     

2D framework materials for energy applications

In recent years a massive increase in publications on conventional 2D materials (graphene, h-BN, MoS₂) is documented, accompanied by the transfer of the 2D concept to porous (crystalline) materials, such as ordered 2D layered polymers, covalent-organic frameworks, and metal–organic frameworks. Over the years, the 3D frameworks have gained a lot of attention for use in applications, ranging from electronic devices to catalysis, and from information to separation technologies, mostly due to the modular construction concept and exceptionally high porosity. A key challenge lies in the implementation of these materials into devices arising from the deliberate manipulation of properties upon delamination of their layered counterparts, including an increase in surface area, higher diffusivity, better access to surface sites and a change in the band structure. Within this minireview, we would like to highlight recent achievements in the synthesis of 2D framework materials and their advantages for certain applications, and give some future perspectives.

In recent years the 2D concept has been transferred from conventional 2D materials to porous 2D framework materials. This minireview takes a closer look onto the preparation of 2D framework materials and their merits for energy applications.     

High-performance polymer field-effect transistors: from the perspective of multi-level microstructures

The multi-level microstructure of conjugated polymers is the most critical parameter determining the charge transport property in field-effect transistors (FETs). However, controlling the hierarchical microstructures and the structural evolution remains a significant challenge. In this perspective, we discuss the key aspects of multi-level microstructures of conjugated polymers towards high-performance FETs. We highlight the recent progress in the molecular structures, solution-state aggregation, and polymer crystal structures, representing the multi-level microstructures of conjugated polymers. By tuning polymer hierarchical microstructures, we attempt to provide several guidelines for developing high-performance polymer FETs and polymer electronics.

The multi-level microstructures of conjugated polymers, including solution-state aggregation and crystal structures, are reviewed due to their influence on charge transport in polymer field-effect transistors.     

Enzyme-activatable fluorescent probes for β-galactosidase: from design to biological applications

β-Galactosidase (β-gal), a typical hydrolytic enzyme, is a vital biomarker for cell senescence and primary ovarian cancers. Developing precise and rapid methods to monitor β-gal activity is crucial for early cancer diagnoses and biological research. Over the past decade, activatable optical probes have become a powerful tool for real-time tracking and in vivo visualization with high sensitivity and specificity. In this review, we summarize the latest advances in the design of β-gal-activatable probes via spectral characteristics and responsiveness regulation for biological applications, and particularly focus on the molecular design strategy from turn-on mode to ratiometric mode, from aggregation-caused quenching (ACQ) probes to aggregation-induced emission (AIE)-active probes, from near-infrared-I (NIR-I) imaging to NIR-II imaging, and from one-mode to dual-mode of chemo-fluoro-luminescence sensing β-gal activity.

This review highlights the molecular design strategy of β-galactosidase-activatable probes from turn-on mode to ratiometric mode, from ACQ to AIE-active probes, from NIR-I to NIR-II imaging and dual-mode of chemo-fluoro-luminescence imaging.     

Local probe investigation of electrocatalytic activity

As the world energy crisis remains a long-term challenge, development and access to renewable energy sources are crucial for a sustainable modern society. Electrochemical energy conversion devices are a promising option for green energy supply, although the challenge associated with electrocatalysis have caused increasing complexity in the materials and systems, demanding further research and insights. In this field, scanning probe microscopy (SPM) represents a specific source of knowledge and understanding. Thus, our aim is to present recent findings on electrocatalysts for electrolysers and fuel cells, acquired mainly through scanning electrochemical microscopy (SECM) and other related scanning probe techniques. This review begins with an introduction to the principles of several SPM techniques and then proceeds to the research done on various energy-related reactions, by emphasizing the progress on non-noble electrocatalytic materials.

Investigation of electrocatalytic materials with scanning probe techniques (SECM, SICM, SECCM and AFM) for energy storage and conversion devices.     

Isomeric anthracene diimide polymers

N-type semiconducting polymers are attractive for organic electronics, but desirable electron-deficient units for synthesizing such polymers are still lacking. As a cousin of rylene diimides such as naphthalene diimide (NDI) and perylene diimide (PDI), anthracene diimide (ADI) is a promising candidate; its polymers, however, have not been achieved yet because of synthetic challenges for its polymerizable monomers. Herein, we present ingenious synthesis of two dibromide ADI monomers with dibromination at differently symmetrical positions of the ADI core, which are further employed to construct ADI polymers. More interestingly, the two obtained ADI polymers possess the same main-chain and alkyl-chain structures but different backbone conformations owing to varied linking positions between repeating units. This feature enables their different optoelectronic properties and film-state packing behavior. The ADI polymers offer first examples of conjugated polymer conformational isomers and are highly promising as a new class of n-type semiconductors for various organic electronics applications.

Two anthracene diimide (ADI) polymers with the backbone conformational isomerism, new members of aromatic diimide polymers family, have been synthesized as a class of highly promising n-type semiconductors for organic electronics.     

Fluorescent small organic probes for biosensing

Small-molecule based fluorescent probes are increasingly important for the detection and imaging of biological signaling molecules due to their simplicity, high selectivity and sensitivity, whilst being non-invasive, and suitable for real-time analysis of living systems. With this perspective we highlight sensing mechanisms including Förster resonance energy transfer (FRET), intramolecular charge transfer (ICT), photoinduced electron transfer (PeT), excited state intramolecular proton transfer (ESIPT), aggregation induced emission (AIE) and multiple modality fluorescence approaches including dual/triple sensing mechanisms (DSM or TSM). Throughout the perspective we highlight the remaining challenges and suggest potential directions for development towards improved small-molecule fluorescent probes suitable for biosensing.

Small-molecule based fluorescent probes are increasingly important for the detection and imaging of biological signaling molecules due to their simplicity, high selectivity and sensitivity, whilst being non-invasive, and suitable for real-time analysis of living systems.     

Controlling the alignment of 1D nanochannel arrays in oriented metal–organic framework films for host–guest materials design

Controlling the direction of molecular-scale pores enables the accommodation of guest molecular-scale species with alignment in the desired direction, allowing for the development of high-performance mechanical, thermal, electronic, photonic and biomedical organic devices (host–guest approach). Regularly ordered 1D nanochannels of metal–organic frameworks (MOFs) have been demonstrated as superior hosts for aligning functional molecules and polymers. However, controlling the orientation of MOF films with 1D nanochannels at commercially relevant scales remains a significant challenge. Here, we report the fabrication of macroscopically oriented films of Cu-based pillar-layered MOFs having regularly ordered 1D nanochannels. The direction of 1D nanochannels is controllable by optimizing the crystal growth process; 1D nanochannels align either perpendicular or parallel to substrates, offering molecular-scale pore arrays for a macroscopic alignment of functional guest molecules in the desired direction. Due to the fundamental interest and widespread technological importance of controlling the alignment of functional molecules and polymers in a particular direction, orientation-controllable MOF films will open up the possibility of realising the potential of MOFs in advanced technologies.

Orientation-controlled Cu₂(Linker)₂DABCO MOF films on macroscopic scales are fabricated for the development of high-performance devices; the direction of 1D nanochannels is controllable either perpendicular or parallel to substrates.     

Extraordinary electrochemical stability and extended polaron delocalization of ladder-type polyaniline-analogous polymers

Electrochemical stability and delocalization of states critically impact the functions and practical applications of electronically active polymers. Incorporation of a ladder-type constitution into these polymers represents a promising strategy to enhance the aforementioned properties from a fundamental structural perspective. A series of ladder-type polyaniline-analogous polymers are designed as models to test this hypothesis and are synthesized through a facile and scalable route. Chemical and electrochemical interconversions between the fully oxidized pernigraniline state and the fully reduced leucoemeraldine state are both achieved in a highly reversible and robust manner. The protonated pernigraniline form of the ladder polymer exhibits unprecedented electrochemical stability under highly acidic and oxidative conditions, enabling the access of a near-infrared light-absorbing material with extended polaron delocalization in the solid-state. An electrochromic device composed of this ladder polymer shows distinct switching between UV- and near-infrared-absorbing states with a remarkable cyclability, meanwhile tolerating a wide operating window of 4 volts. Taken together, these results demonstrate the principle of employing a ladder-type backbone constitution to impart superior electrochemical properties into electronically active polymers.

Electrochemical stability and state delocalization critically impact the functions and practical applications of electronically active polymers.     

Challenges and prospects of ambient hybrid solar cell applications

The impending implementation of billions of Internet of Things and wireless sensor network devices has the potential to be the next digital revolution, if energy consumption and sustainability constraints can be overcome. Ambient photovoltaics provide vast universal energy that can be used to realise near-perpetual intelligent IoT devices which can directly transform diffused light energy into computational inferences based on artificial neural networks and machine learning. At the same time, a new architecture and energy model needs to be developed for IoT devices to optimize their ability to sense, interact, and anticipate. We address the state-of-the-art materials for indoor photovoltaics, with a particular focus on dye-sensitized solar cells, and their effect on the architecture of next generation IoT devices and sensor networks.

The impending implementation of billions of Internet of Things and wireless sensor network devices has the potential to be the next digital revolution, if energy consumption and sustainability constraints can be overcome.     

Supramolecular strategies in artificial photosynthesis

Artificial photosynthesis is a major scientific endeavor aimed at converting solar power into a chemical fuel as a viable approach to sustainable energy production and storage. Photosynthesis requires three fundamental actions performed in order; light harvesting, charge-separation and redox catalysis. These actions span different timescales and require the integration of functional architectures developed in different fields of study. The development of artificial photosynthetic devices is therefore inherently complex and requires an interdisciplinary approach. Supramolecular chemistry has evolved to a mature scientific field in which programmed molecular components form larger functional structures by self-assembly processes. Supramolecular chemistry could provide important tools in preparing, integrating and optimizing artificial photosynthetic devices as it allows precise control over molecular components within such a device. This is illustrated in this perspective by discussing state-of-the-art devices and the current limiting factors – such as recombination and low stability of reactive intermediates – and providing exemplary supramolecular approaches to alleviate some of those problems. Inspiring supramolecular solutions such as those discussed herein will incite expansion of the supramolecular toolbox, which eventually may be needed for the development of applied artificial photosynthesis.

This review describes supramolecular strategies for optimization and integration of components needed for the fundamentals of artificial photosynthesis: light harvesting, charge-separation and catalysis, which are relevant for solar-to-fuel devices.     

One stone,three birds: one AIEgen with three colors for fast differentiation of three pathogens

Visually identifying pathogens favors rapid diagnosis at the point-of-care testing level. Here, we developed a microenvironment-sensitive aggregation-induced emission luminogen (AIEgen), namely IQ–Cm, for achieving fast discrimination of Gram-negative bacteria, Gram-positive bacteria and fungi by the naked-eye. With a twisted donor–acceptor and multi-rotor structure, IQ–Cm shows twisted intramolecular charge transfer (TICT) and AIE properties with sensitive fluorescence color response to the microenvironment of pathogens. Driven by the intrinsic structural differences of pathogens, IQ–Cm with a cationic isoquinolinium moiety and a membrane-active coumarin unit as the targeting and interacting groups selectively locates in different sites of three pathogens and gives three naked-eye discernible emission colors. Gram-negative bacteria are weak pink, Gram-positive bacteria are orange-red and fungi are bright yellow. Therefore, based on their distinctive fluorescence response, IQ–Cm can directly discriminate the three pathogens at the cell level under a fluorescence microscope. Furthermore, we demonstrated the feasibility of IQ–Cm as a visual probe for fast diagnosis of urinary tract infections, timely monitoring of hospital-acquired infection processes and fast detection of molds in the food field. This simple visualization strategy based on one single AIEgen provides a promising platform for rapid pathogen detection and point-of-care diagnosis.

A simple AIEgen with three emission colors achieves rapid identification of Gram-negative bacteria, Gram-positive bacteria and fungi.     

Interfacial growth of free-standing PANI films: toward high-performance all-polymer supercapacitors

Along with high power capability and energy density, long cycle life is regarded an essential performance requirement for energy storage devices. The rapid capacitance decline of conducting polymer-based electrodes remains a major technical challenge and precludes their practical applications in supercapacitors. In this work, a polyaniline (PANI) network is synthesized via interfacial Buchwald–Hartwig polymerization for the first time, facilitating the construction of covalently connected PANI networks by ligand-promoted C–N bond formation. Particularly, the interfacial synthesis and subsequent gas release from pre-anchored protecting groups allow bottom-up and efficient access to porous cross-linked PANI (PCL-PANI) films that are free-standing and solvent-resistant. Upon assembling into supercapacitors, the PCL-PANI material enables an unprecedent long-term charge–discharge cycling performance (>18 000 times) without clear capacitance loss for an additive-free pseudocapacitive system. In addition, this synthesis affords electrodes entirely consisting of conducting polymers, yielding highly reversible gravimetric capacitance at 435 F g_electrode⁻¹ in a two-electrode system, and a high gravimetric energy of 12.5 W h kg_electrode⁻¹ while delivering an outstanding power density of 16 000 W kg_electrode⁻¹, which is 10-fold higher than those of conventional linear PANI composite supercapacitors. This synthetic approach represents a novel and versatile strategy to generate additive/binder-free and high-performance conducting thin-films for energy storage.

A covalently cross-linked polyaniline network is synthesized via interfacial Buchwald-Hartwig polymerization/deprotection, enabling the generation of additive/binder-free and high-performance conducting thin-films for energy storage.      

Using fluorene to lock electronically active moieties in thermally activated delayed fluorescence emitters for high-performance non-doped organic light-emitting diodes with suppressed roll-off

Thermally activated delayed fluorescence (TADF) emitters with aggregation-induced emission (AIE) features are hot candidates for non-doped organic light-emitting diodes (OLEDs), as they are highly emissive in solid states upon photoexcitation. Nevertheless, not every AIE-TADF emitter in the past had guaranteed decent efficiencies in non-doped devices, indicating that the AIE character alone does not necessarily afford ideal non-doped TADF emitters. As intermolecular electron-exchange interaction that involves long-lived triplet excitons plays a dominant role in the whole quenching process of TADF, we anticipate that it is the main reason for the different electroluminescence performances of AIE-TADF emitters. Therefore, in this work, we designed two TADF emitters SPBP-DPAC and SPBP-SPAC by modifying a reported less successful emitter BP-DPAC with extra fluorenes to increase intermolecular distances and attenuate this electron-exchange interaction. With the fluorene lock as steric hindrance, SPBP-DPAC and SPBP-SPAC exhibit significantly higher exciton utilization in non-doped films due to the suppressed concentration quenching. The non-doped OLEDs based on SPBP-DPAC and SPBP-SPAC show an excellent maximum external quantum efficiency (EQE) of 22.8% and 21.3% respectively, and what''s even more promising is that ignorable roll-offs at practical brightness (e.g., 1000 and 5000 cd m⁻²) were realized. These results reveal that locking the phenyl rings as steric hindrance can not only enhance the molecular rigidity, but also cause immediate relief of concentration quenching, and result in significant performance improvement under non-doped conditions. Our approach proposes a feasible molecular modification strategy for AIE-TADF emitters, potentially increasing their applicability in OLEDs.

Two TADF emitters were developed by modifying a reported less successful emitter BP-DPAC with fluorene to suppress concentration quenching. Their non-doped OLEDs displayed excellent EQEs of 22.8% and 21.3% with well-suppressed roll-off.     

Covalent cell surface recruitment of chemotherapeutic polymers enhances selectivity and activity

Synthetic macromolecular chemotherapeutics inspired by host defence peptides can disrupt cell membranes and are emerging as agents for the treatment of cancer and infections. However, their off-target effects remain a major unmet challenge. Here we introduce a covalent recruitment strategy, whereby metabolic oligosaccharide engineering is used to label targeted cells with azido glycans, to subsequently capture chemotherapeutic polymers by a bio-orthogonal click reaction. This results in up to 10-fold reduction in EC₅₀ and widening of the therapeutic window. Cell death is induced by not only membrane leakage, but also by apoptosis due to the conjugated chemotherapeutic being internalised by glycan recycling. Covalent recruitment also lead to increased penetration and significant cell death in a 3-D tumour model in just 3 hours, whereas doxorubicin required 24 hours. This conceptual approach of ‘engineering cells to capture polymers’ rather than ‘engineering polymers to target cells’ will bring new opportunities in non-traditional macromolecular therapeutics.

Chemotherapeutic polymers are targeted to cells by introduction of unnatural glycans to their glycocalyx, enhancing their cytotoxic effect.