Thiophene π-bridge-based second near-infrared luminogens with aggregation-induced emission for biomedical applications.

In the past 5 years, aggregation-induced emission luminogens (AIEgens) with emission in the second near-infrared (NIR-II) optical window have aroused great interest in bioimaging and disease phototheranostics, benefiting from the merits of deep penetration depth, reduced light scatting, high spatial resolution, and minimal photodamage. To construct NIR-II AIEgens, thiophene derivatives are frequently adopted as π-bridge by virtue of their electron-rich feature and good modifiability. Herein, we summarize the recent progress of NIR-II AIEgens by employing thiophene derivatives as π-bridge mainly compassing unsubstituted thiophene, alkyl thiophene, 3,4-ethylenedioxythiophene, and benzo[c]thiophene, with a discussion on their structure-property relationships and biomedical applications. Finally, a brief conclusion and perspective on this fascinating area are offered.

An AIE Metal Iridium Complex: Photophysical Properties and Singlet Oxygen Generation Capacity.

Photodynamic therapy (PDT) has garnered significant attention in the fields of cancer treatment and drug-resistant bacteria eradication due to its non-invasive nature and spatiotemporal controllability. Iridium complexes have captivated researchers owing to their tunable structure, exceptional optical properties, and substantial Stokes displacement. However, most of these complexes suffer from aggregation-induced quenching, leading to diminished luminous efficiency. In contrast to conventional photosensitizers, photosensitizers exhibiting aggregation-induced luminescence (AIE) properties retain the ability to generate a large number of reactive oxygen species when aggregated. To overcome these limitations, we designed and synthesized a novel iridium complex named Ir-TPA in this study. It incorporates quinoline triphenylamine cyclomethylated ligands that confer AIE characteristics for Ir-TPA. We systematically investigated the photophysical properties, AIE behavior, spectral features, and reactive oxygen generation capacity of Ir-TPA. The results demonstrate that Ir-TPA exhibits excellent optical properties with pronounced AIE phenomenon and robust capability for producing singlet oxygen species. This work not only introduces a new class of metal iridium complex photosensitizer with AIE attributes but also holds promise for achieving remarkable photodynamic therapeutic effects in future cellular experiments and biological studies.

Near-Infrared Afterglow ONOO--Triggered Nanoparticles for Real-Time Monitoring and Treatment of Early Ischemic Stroke.

Early detection and drug intervention with the appropriate timing and dosage are the main clinical challenges for ischemic stroke (IS) treatment. The conventional therapeutic agents relay fluorescent signals, which require real-time external light excitation, thereby leading to inevitable autofluorescence and poor tissue penetration. Herein, we report endogenous peroxynitrite (ONOO-)-activated BDP-4/Cur-CL NPs that release NIR afterglow signals (λmax 697 nm) for real-time monitoring of the progression of ischemia reperfusion (I/R) brain injury while releasing curcumin for the safe treatment of IS. The BDP-4/Cur-CL NPs exhibited bright NIR afterglow luminescence (maximum 732-fold increase), superb sensitivity (LOD = 82.67 nM), high energy-transfer efficiency (94.6%), deep tissue penetration (20 mm), outstanding antiapoptosis, and anti-inflammatory effects. The activated NIR afterglow signal obtained in mice with middle cerebral artery occlusion (MCAO) showed three functions: (i) the BDP-4/Cur-CL NPs are rapidly activated by endogenous ONOO-, instantly illuminating the lesion area, distinguishing I/R damage from normal areas, which can be successfully used for endogenous ONOO- detection in the early stage of IS; (ii) real-time reporting of in situ generation and dynamic fluctuations of endogenous ONOO- levels in the lesion area, which is of great value in monitoring the evolutionary mechanisms of IS; and (iii) dynamic monitoring of the release of curcumin drug for safe treatment. Indeed, the released curcumin effectively decreased apoptosis, enhanced survival, alleviated neuroinflammation, reduced brain tissue loss, and improved the cognition of MCAO stroke mice. This work is the first example of afterglow luminescence for early diagnosis, real-time reporting, drug tracing, and treatment for IS.

Recent advances of AIE-active materials for orthotopic tumor phototheranostics.

Cancer ranks as a leading threat to human life and health. Compared to conventional cancer treatments, phototheranostics shares the advantages of integrated diagnosis and therapy, outstanding therapeutic performance and good controllability. Amid diverse phototheranostic agents, small organic luminogens with aggregation-induced emission (AIEgen) tendency show predominant advantages in terms of superior photostability, large Stokes shifts, and boosted theranostic capacity as aggregates. In the past two decades, AIE-active materials have demonstrated formidable applications in disease theranostics, especially for tumors. This review mainly highlights the recent advances of orthotopic tumor phototheranostics mediated by AIEgens with a classification of different organs. Additionally, a brief discussion of current bottlenecks and future directions is outlined. We believe this review can deepen the understanding and spur more innovations on tumor theranostics by employing AIEgens. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Self-assembled nanoparticles based on cationic mono-/AIE tetra-nuclear Ir(III) complexes: long wavelength absorption/near-infrared emission photosensitizers for photodynamic therapy.

Cyclometalated Ir(III) complexes as photosensitizers (PSs) have attracted widespread attention because of their good photostability and efficient 1O2 production ability. However, their strong absorption in the UV-vis region severely limits their applications in photodynamic therapy (PDT) because the short wavelength illuminating light can be easily absorbed by the skin and subcutaneous adipose tissue causing damage to the patient's normal tissue. Herein, mono- and tetra-nuclear Ir(III) complex-porphyrin conjugates are rationally designed and synthesized, especially [TPP-4Ir]4+ exhibits obvious aggregation-induced emission (AIE) characteristics. PSs comprising Ir(III) complex-porphyrin conjugates self-assembled as nanoparticles (NPs) are successfully achieved. The obtained [TPP-Ir]+ NPs and [TPP-4Ir]4+ NPs exhibit long wavelength absorption (500-700 nm) and near-infrared emission (635-750 nm), successfully overcoming the inherent defects of short wavelength absorption of traditional Ir(III) complexes. Moreover, [TPP-4Ir]4+ NPs exhibit good biocompatibility, high 1O2 generation ability, low half-maximal inhibitory concentration (IC50) (0.47 × 10-6 M), potent cytotoxicity toward cancer cells and superior cellular uptake under white light irradiation. This work extends the scope for transition metal complex PSs with promising clinical applications.

Ir(III) Complexes with AIE Characteristics for Biological Applications.

Both biological process detection and disease diagnosis on the basis of luminescence technology can provide comprehensive insights into the mechanisms of life and disease pathogenesis and also accurately guide therapeutics. As a family of prominent luminescent materials, Ir(III) complexes with aggregation-induced emission (AIE) tendency have been recently explored at a tremendous pace for biological applications, by virtue of their various distinct advantages, such as great stability in biological media, excellent fluorescence properties and distinctive photosensitizing features. Significant breakthroughs of AIE-active Ir(III) complexes have been achieved in the past few years and great progress has been witnessed in the construction of novel AIE-active Ir(III) complexes and their applications in organelle-specific targeting imaging, multiphoton imaging, biomarker-responsive bioimaging, as well as theranostics. This review systematically summarizes the basic concepts, seminal studies, recent trends and perspectives in this area.

AIE-active Ir(III) complexes functionalised with a cationic Schiff base ligand: synthesis, photophysical properties and applications in photodynamic therapy.

Photodynamic therapy (PDT) is a promising cancer treatment method. Traditional small-molecule photosensitizers (PSs) suffer from low intersystem crossing (ISC) ability and aggregation-caused quenching (ACQ), which adversely affects the luminous efficiency and singlet oxygen (1O2) yield of PSs in the aggregated state. Ir(III) complexes are promising PSs with long excited-state lifetime, good photophysical and photochemical properties and large Stokes shifts. Aggregation-induced emission (AIE) characteristics could reduce the nonradiative recombination and improve the ISC ability of excited states through the restriction of the intramolecular motions in aggregated states. Accordingly, two AIE-active Ir(III) complexes Ir-1-N+ and Ir-2-N+ were successfully designed and obtained based on Schiff base ligands. Experimental results showed that Ir-1-N+ and Ir-2-N+ have good photophysical properties and the corresponding nanoparticles (NPs) have good water solubility and 1O2 generation ability. Notably, Ir-2-N+ NPs can be efficiently taken up by mouse breast cancer cells (4T1 cells) with good biocompatibility, low dark toxicity and excellent phototoxicity. This work demonstrates a versatile strategy for exploiting efficient transition metal PSs with a cationic ligand in PDT.

AIE-active iridium(III) complex integrated with upconversion nanoparticles for NIR-irradiated photodynamic therapy.

The integration of an aggregation induced emission (AIE)-active Ir(III) complex and upconversion nanoparticles (UCNPs) has achieved a NIR-irradiated photosensitizer (PS), UCNPs@Ir-2-N. This PS has satisfactory biocompatibility, excellent phototoxicity, good accumulation in cells and high 1O2 generation ability, thereby effectively killing 4T1 mouse cancer cells in vitro. This work has potential for future photodynamic therapy (PDT) applications.

LncRNA CRNDE exacerbates neuropathic pain in chronic constriction injury-induced(CCI) rats through regulating miR-146a-5p/WNT5A pathway.

Neuropathic pain (NP) originating from a dysfunction in the nervous system is often intractable and chronic. Many studies have implicated long noncoding RNAs (lncRNAs) in the physiological and pathological development of NP. The lncRNA colorectal neoplasia differentially expressed gene (CRNDE) has been shown to mediate NP progression. However, further investigations are needed to gain deeper understanding of the specific mechanisms governing CRNDE in NP etiopathology. In this study, we successfully used chronic constrictive injury (CCI)-induced rats to establish an NP model with intrathecal injection, and confirmed the upregulation of CRNDE in CCI-induced rats. Moreover, silencing of CRNDE relieved mechanical allodynia, thermal hyperalgesia, and neuroinflammation in the NP model. Bioinformatics analysis predicted that miR-146a-5p binds to CRNDE. Our findings validated that miR-146a-5p was a target of CRNDE and that the expression of miR-146a-5p was decreased in CCI rats. Furthermore, miR-151A-3p was found to exert a negative regulatory effect on WNT5A. In addition, knockdown of WNT5A alleviated the pain-related behavior and inflammatory response of NP in vivo. Finally, we demonstrated that CRNDE contributed to the progression of CCI-induced NP via competitive binding to miR-146a-5p to upregulate WNT5A. The present study offers novel insights that may be translated into improved therapies for NP.

Ir(III) Complex Dimer Nanoparticles for Photodynamic Therapy.

Iridium compounds are versatile in catalysis and photodynamic therapy. We present two Ir(III) complex dimers that can self-assemble into nanoparticles in the absence of adjuvant or surfactants. The formed nanoparticles possess a spherical morphology and robust colloidal stability and could be internalized by cancer cells. The Ir(III) complex nanoparticles have relatively strong photodynamic activity upon irradiation, which includes type I and type II reactive oxygen species. The generated reactive oxygen species could effectively induce cell death upon irradiation. This work highlights the potential of metal complexes and their nanoparticles in cancer treatment.

Tunable Dual-Color Emission Perovskites via Post-Synthetic Modification Strategy for Near-Unity Photoluminescence Quantum Yield.

Lead halide perovskites (LHPs) with excellent performance have become promising materials for optoelectrical devices. However, as for the dual-color emission LHPs (DELHPs), the low photoluminescence quantum yield (PLQY) hinders their applications. Herein, a simple low-cost room-temperature post-synthetic modification strategy is used to achieve a near-unity PLQY of DELHPs. It is proven that ZnBr2 plays an important role as an inorganic ligand in reducing surface defects to induce a 95.4% increase in the radiative decay rate and a 99.5% decrease in the nonradiative decay rate in the treated DELHPs compared with the pristine DELHPs. The performance of the blue emission from the surface lattice is greatly improved via the modification of ZnBr2. DELHPs with different ratios of blue and green emissions are obtained by changing the specific surface area and ZnBr2 concentration. The distribution and mechanism of Zn2+ are discussed using the research model based on these DELHPs. The first example of the single-layer dual-color perovskite electroluminescence device is realized from DELHPs. This work provides a new perspective for improving the performance of DELHPs, which will greatly accelerate the development of emission materials of LHPs.

Understanding Mechanochromic Luminescence on Account of Molecular Level Based on Phosphorescent Iridium(III) Complex Isomers.

Mechanochromic luminescent (MCL) materials are promising in pressure sensors, security papers, photoelectric devices and optical data recording. Although some kinds of MCL-active iridium(III) complexes with various soft substituent functional ligands (e.g., dendritic carbazole, flexible chains, and Schiff base ligands) were reported, the MCL mechanism is still not clear and mainly ascribes to the physical phase transformations from crystalline state to amorphous state in response to force stimulus at present stage, and deserves further study in order to obtain more intelligent MCL materials. Herein, two new iridium(III) complex isomers are tactfully constructed and show distinctly opposite MCL properties in spite of the same physical phase transformations happening on them. The absolutely out of the ordinary MCL mechanism has been presented on account of molecular level for the first time via the comparative study of photophysical properties based on isomers 1 and 2 with the help of crystal structure analysis, room/low temperature emission spectra, NMR, PXRD, and TD-DFT calculations. All of these results suggest that the emitting state dominated by the triplet charge transfer excited state (3CT) plays a key role in achieving mechanochromic luminescence in iridium(III) complex systems.

Rational design of iridium-porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents.

Near-infrared (NIR) emitters are important probes for biomedical applications. Nanoparticles (NPs) incorporating mono- and tetranuclear iridium(iii) complexes attached to a porphyrin core have been synthesized. They possess deep-red absorbance, long-wavelength excitation (635 nm) and NIR emission (720 nm). TD-DFT calculations demonstrate that the iridium-porphyrin conjugates herein combine the respective advantages of small organic molecules and transition metal complexes as photosensitizers (PSs): (i) the conjugates retain the long-wavelength excitation and NIR emission of porphyrin itself; (ii) the conjugates possess highly effective intersystem crossing (ISC) to obtain a considerably more long-lived triplet photoexcited state. These photoexcited states do not have the usual radiative behavior of phosphorescent Ir(iii) complexes, and they play a very important role in promoting the singlet oxygen (1O2) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high 1O2 generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC50) (0.057 µM), excellent photothermal imaging and synergistic PDT and PTT under 635 nm laser irradiation. To our knowledge this is the first example of iridium-porphyrin conjugates as PSs for photothermal imaging-guided synergistic PDT and PTT treatment in vivo.

Near-infrared-emitting AIE multinuclear cationic Ir(III) complex-assembled nanoparticles for photodynamic therapy.

Near-infrared (NIR) emission and impressive singlet oxygen (1O2) generation ability are highly desirable but remain difficult to realize as aggregation-induced emission (AIE) photosensitizers (PSs). Herein, mono- and tri-nuclear NIR AIE cationic Ir(iii) complexes and their corresponding self-assembled nanoparticles (NPs) without any surfactants or adjuvants were designed and synthesized by integrating rigid 1,3,5-triphenyl benzene as an extended π-conjugation bridge. The pure NPs exhibit multiple merits of stronger NIR emission, higher 1O2 production capacity, better water solubility and negligible dark toxicity compared with the Ir(iii) complexes. Notably, the AIE PS3 NPs possess bright NIR emission at 730 nm, suitable spherical sizes below 100 nm, favorable cellular uptake and superior phototoxicity (IC50 = 1.4 × 10-6 M). These are the first pure NIR-emitting multinuclear Ir(iii) complex NPs obtained by self-assembly that exhibit excellent cell imaging and photodynamic therapy (PDT) performance.

A mechanochromic cyclemetalated cationic Ir(iii) complex with AIE activity by strategic modification of ligands.

Two new aggregation-induced emission (AIE)-active cyclemetalated cationic Ir(iii) complexes have been rationally designed and synthesized by introducing O-H substituents into Schiff base ligands. π-Hydrogen bonding is successfully exploited for the first time to realize the mechanochromic luminescence (MCL) property by the synergistic effect of O-H and F substituents in complex 1. An X-ray crystal structure analysis of the two complexes suggests that the intramolecular hydrogen bonding effectively restricted the molecular motions, thus causing typical AIE characteristics. More importantly, a loosely packed structure constructed from intermolecular hydrogen bonding interactions (O-Hπ and C-HF) is obtained, and it is susceptible to mechanical stimulation. Powder X-ray diffraction (PXRD) studies also prove that the MCL behavior of complex 1 is caused by the reversible phase transition from crystalline to amorphous state under grinding and solvent recrystallization, leading to a change in emission colors. A re-writable phosphorescence data recording device was fabricated using complex 1 as the active material. Our molecular design strategies provide a new avenue for achieving efficient phosphorescence materials with AIE and MCL properties.

Supramolecular Oligourethane Gel with Multicolor Luminescence Controlled by Mechanically Sensitive Hydrogen-Bonding.

We report a new type of mechanically sensitive multicolor luminescent oligourethane gel (OUA-gel). The conformation of the oligomeric chains can be controlled by changing the strength of hydrogen bonds. The optical properties of the oligomers are highly dependent on the conformations which vary in response to mechanical stresses and phase transitions. The design relies on the introduction of a single mechanical chromophore, aurintricarboxylic acid, with propeller-like, spatially crowded, and highly twisted conformations, and the presence of three carboxyl groups, which provide multidirectional hydrogen-bonding opportunities. Introducing dimethylsulfoxide (DMSO) as an additional H-bond acceptor molecule leads to a viscous OUA-gel which exhibits multiemission colors because of changes in the chain conformation within the matrix, which are induced by different strengths of H bonds. The conformation can be adjusted by mechanical force or temperature, both of which influence the H-bonding. The multifunctional and multicolored mechanochromism of the OUA-gel has great promise in sensing applications. The results represent a substantial step toward understanding the mechanism of polychromism in soft materials and the molecular design of advanced smart materials.

Water-soluble cyclometalated Ir(III) complexes as carrier-free and pure nanoparticle photosensitizers for photodynamic therapy and cell imaging.

Herein, we provide a new and facile strategy to successfully overcome the inherent aggregation-caused quenching effect and hydrophobicity that exist in traditional PSs by the introduction of sodium salts. The obtained water-soluble Ir(iii) complexes as carrier-free and pure nanoparticle photosensitizers exhibit excellent performance in photodynamic therapy and cell imaging.

Dinuclear metal complexes: multifunctional properties and applications.

The development of metal complexes for optoelectronic applications is a fertile area of research. In contrast to the rigorous development of mononuclear metal complexes, dinuclear species have been less well studied and their fundamental chemistry and applications are under-explored. However, dinuclear species present special properties and functions compared with mononuclear species as a consequence of tuning the bridging ligands, the cyclometalated ligands or the two metal centers. More recently, dinuclear species have enabled important breakthroughs in the fields of OLEDs, photocatalytic water splitting and CO2 reduction, DSPEC, chemosensors, biosensors, PDT, smart materials and so on. Here we present an overview of recent developments of dinuclear metal complexes, their multifunctional properties and their various applications. The relationship between structure and property of dinuclear species and important factors which influence device performance are discussed. Finally, we illustrate some challenges and opportunities for future research into dinuclear metal complexes. This review aims to provide an up-to-date summary and outlook of functional dinuclear metal complexes and to stimulate more researchers to contribute to this exciting interdisciplinary field.

Bright red aggregation-induced emission nanoparticles for multifunctional applications in cancer therapy.

Developing multifunctional photosensitizers (PSs) is needed to effectively simplify cancer treatment, but it remains a big challenge. Here, two red-emitting AIE-active, donor-acceptor (D-A) PSs with small ΔE ST and their AIE nanoparticles, are rationally designed and synthesized. The PS1 NPs exhibit bright red-emission with high quantum yield, appropriate 1O2 generation ability and good biocompatibility. More importantly, PS1 NPs can strongly light up the cytoplasm by gently shaking the cells for only 5 s at room temperature, indicating ultrafast staining and mild incubation conditions. In vitro and in vivo cell tracing demonstrate that PS1 NPs can track cells over 14 days, and effectively inhibit tumor growth upon irradiation. To the best of our knowledge, this work is the first example of a PS that integrates image-guided PDT, ultrafast staining and long-term tracing functions, demonstrating the "all-in-one" concept which offers great advantages for potential clinical applications.

Reversible tricolour luminescence switching based on a piezochromic iridium(iii) complex.

On the basis of rational molecular design, the tricolour luminescence switching of an Ir(iii) complex is achieved for the first time. The transformation between two crystalline states and an amorphous state is responsible for the switching behaviour of this complex between blue, green and yellow states. Solvent molecules are shown to play a crucial role in the crystallization and luminescence processes.