Visualization of the brain in its native environment is important for understanding common brain diseases. Herein, bright luminogens with remarkable aggregation‐induced emission (AIE) characteristics ...and high quantum yields of up to 42.6% in the solid state are synthesized through facile reaction routes. The synthesized molecule, namely BTF, shows ultrabright far‐red/near‐infrared emission and can be fabricated into AIE dots by a simple nanoprecipitation procedure. Due to their high brightness, large Stokes shift, good biocompatibility, satisfactory photostability, and large three‐photon absorption cross section, the AIE dots can be utilized as efficient fluorescent nanoprobes for in vivo brain vascular imaging through the intact skull by a three‐photon fluorescence microscopy imaging technique. This is the first example of using AIE dots for the visualization of the cerebral stroke process through the intact skull of a mouse with high penetration depth and good image contrast. Such good results are anticipated to open up a new venue in the development of efficient emitters with strong nonlinear optical effects for noninvasive bioimaging of living brain.
An ultrabright solid‐state FR/NIR luminogen with aggregation‐induced emission (AIE) feature is reported. Its resulting AIE dots show good biocompatibility, satisfactory photostability, and a large three‐photon absorption cross section. The AIE dots are reported for visualization of the cerebral thrombosis process of a mouse with intact skull, with high penetration depth and good image contrast.
The synthesis of water-soluble near-infrared (NIR)-emissive fluorescent molecules with aggregation-induced emission (AIE) characteristics and theranostic functions is highly desirable but remains ...challenging. In this work, we designed and readily prepared for the first time such a molecule with AIE features, good water-solubility and intense emission in the NIR region. This AIE luminogen (AIEgen) is able to specifically "light up" the cell membrane without the involvement of a washing procedure. Interestingly, the staining process can be performed by simply shaking the culture with cells at room temperature for only a few seconds after the addition of the AIEgen, indicating an ultrafast and easy-to-operate staining protocol. This is the first fluorescent "light-up" probe for cell-imaging that allows the combination of a short staining period (at the second-level) with a wash-free process. Additionally, the presented AIEgen has also been developed to serve as an excellent phototherapeutic agent for high efficiency generation of reactive oxygen species (ROS) upon visible light irradiation, which allows its effective application in the photodynamic ablation of cancer cells, demonstrating its dual role as an imaging and phototherapeutic agent.
Photoactivatable probes for lipid droplets (LDs)-specific live-cell imaging are powerful tools for investigating their biological functions through precise spatial and temporal control. Ideal ...photoactivatable probes for LDs imaging require high concentration accumulation of fluorophores in LDs, simple synthetic procedures, and excellent photoactivation efficiency. However, it is difficult to overcome these challenges by conventional fluorophores due to aggregation-caused quenching (ACQ). In this study, a new class of photoactivatable and LDs-specific fluorescent probes was developed based on dihydro-2-azafluorenones, which can easily undergo photooxidative dehydrogenation reaction to afford 2-azafluorenones with aggregation-induced emission (AIE) properties. Dihydro-2-azafluorenones as photoactivatable and LDs-specific probes display significant advantages of excellent photoactivation efficiency and lack of self-quenching in the aggregated state, and are expected to have broad applications in study of biological functions of LDs' through light-controlled spatiotemporal imaging.
Photosensitizers are light-sensitive molecules that are highly hydrophobic, which poses a challenge to their use for photodynamic therapy. Hence, considerable efforts have been made to develop ...carriers for the delivery of PSs. Herein, we synthesized a new theranostic nanoagent (CQDs@PtPor) through the electrostatic interaction between the tetraplatinated porphyrin complex (PtPor) and the negatively charged CQDs. The size and morphology of as-prepared CQDs and CQDs@PtPor were characterized by a series of methods, such as XRD, TEM, XPS, and FTIR spectroscopy. The CQDs@PtPor composite integrates the optical properties of CQDs and the anticancer function of porphyrin into a single unit. The spectral results suggested the effective resonance energy transfer from CQDs to PtPor in the CQDs@PtPor composite. Impressively, the CQDs@PtPor composite showed the stronger PDT effect than that of organic molecular PtPor, suggesting that CQDs@PtPor is advantageous over the conventional formulation, attributable to the enhanced efficiency of
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production of PtPor by CQDs. Thus, this CQDs-based drug nanocarrier exhibited enhanced tumor-inhibition efficacy as well as low side effects in vitro, showing significant application potential in the cancer therapy.
Cancer is the leading cause of death worldwide. With the advantages of low cost, high sensitivity and ease of accessibility, fluorescence imaging has been widely used for cancer detection in the ...scientific field. Aggregation-induced emission luminogens (AIEgens) are a class of synthesized fluorescent probes with high brightness and photostability in the aggregate state. Herein, a new positively-charged AIEgen, abbreviated as TPE-IQ-2O, is designed and characterized. TPE-IQ-2O not only can distinguish cancer cells from normal cells with high contrast with the aid of the difference in mitochondrial membrane potential as well as the quantity of mitochondria, but it also works as a promising photosensitizer to kill cancer cells through generation of reactive oxygen species upon white light irradiation, thus making it a promising AIE theranostic system.
Silver staining, which exploits the special bioaffinity and the chromogenic reduction of silver ions, is an indispensable visualization method in biology. It is a most popular method for in‐gel ...protein detection. However, it is limited by run‐to‐run variability, background staining, inability for protein quantification, and limited compatibility with mass spectroscopic (MS) analysis; limitations that are largely attributed to the tricky chromogenic visualization. Herein, we reported a novel water‐soluble fluorogenic Ag+ probe, the sensing mechanism of which is based on an aggregation‐induced emission (AIE) process driven by tetrazolate‐Ag+ interactions. The fluorogenic sensing can substitute the chromogenic reaction, leading to a new fluorescence silver staining method. This new staining method offers sensitive detection of total proteins in polyacrylamide gels with a broad linear dynamic range and robust operations that rival the silver nitrate stain and the best fluorescent stains.
Fluorogenic development of silver: Reported is a fluorogenic Ag+ detection system accomplished by a spontaneous tetrazolate–Ag+ aggregation. This system can substitute the tricky chromogenic reduction step of the traditional silver staining methods with a fluorogenic detection step, leading to a sensitive and robust fluorescent visualization of total proteins.
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•A novel AIE molecule was facilely synthesized through a single-step reaction with commercially available materials.•The D-π-A structure endows the AIE molecule with TICT ...characteristic, making it a reversible fluorescent thermometer.•The AIE molecule exhibited good biocompatibility.•The AIE molecule can be used as a probe for lipid droplets-specific imaging and a photosensitizer to kill cancer cells.
Luminogens with aggregation-induced emission (AIE) characteristic drew extraordinary attention owing to their excellent luminescence properties in aggregated state or solid state, which showed wide application prospect in chemical sensing, bioimaging, lighting material and display material. In this work, a novel AIE molecule of (2,3-bis(4-(dimethylamino)phenyl)quinoxalin-6-yl)(phenyl)methanone (designated as LD-red) was facilely synthesized through a single-step reaction with commercially available materials. Based on its intrinsic twisted intramolecular charge transfer (TICT) characteristic, LD-red was successfully utilized as a reversible fluorescent thermometer. More importantly, LD-red exhibited good biocompatibility, which not only can be used as a probe for lipid droplets-specific imaging, but also can work as a promising photosensitizer to kill cancer cells through generation of reactive oxygen species (ROS) upon white light irradiation. LD-red enriches the kinds of AIEgens and, more importantly, this work provides a new strategy for constructing multifunctional AIEgen with TICT characteristic.
The application of fluorescent probes for in vivo retinal imaging is of great importance, which could provide direct and crucial imaging evidence for a better understanding of common eye diseases. ...Herein, a group of bright organic luminogens with typical electron-donating (D) and electron-accepting (A) structures (abbreviated as LDs-BDM, LDs-BTM, and LDs-BHM) was synthesized through a simple single-step reaction. They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70% (e.g., 83.7% for LDs-BTM). Their light-emission properties could be tuned by the modulation of π-conjugation effect with methoxy groups at different substituent positions. Their resulting fluorescent nanoparticles (NPs) were demonstrated as specific lipid droplets (LDs) targeting probes with high brightness, good biocompatibility, and satisfactory photostability. LDs-BTM NPs with a large two-photon absorption cross section (σ2 = 249 GM) were further utilized as ultrabright two-photon fluorescence (2PF) nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration (0.5 µmol/L). Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated. This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique. These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.
The ultrabright organic luminogen (namely LDs-BTM) with specific lipid droplets targeting feature, good biocompatibility, and excellent photostability shows outstanding performance in two-photon fluorescence imaging of the retina in vivo. Display omitted
Background
Interleukin‐15 (IL‐15) is a promising immunotherapeutic agent owing to its powerful immune‐activating effects. However, the clinical benefits of these treatments are limited. Crosstalk ...between tumor cells and immune cells plays an important role in immune escape and immunotherapy drug resistance. Herein, this study aimed to obtain in‐depth understanding of crosstalk in the tumor microenvironment for providing potential therapeutic strategies to prevent tumor progression.
Methods
T‐cell killing assays and co‐culture models were developed to determine the role of crosstalk between macrophages and tumor cells in breast cancer resistant to IL‐15. Western blotting, histological analysis, CRISPR‐Cas9 knockout, multi‐parameter flow cytometry, and tumor cell‐macrophage co‐injection mouse models were developed to examine the mechanism by which IL‐15Rα+ tumor‐associated macrophages (TAMs) regulate breast cancer cell resistance to IL‐15.
Results
We found that macrophages contributed to the resistance of tumor cells to IL‐15, and tumor cells induced macrophages to express high levels of the α subunit of the IL‐15 receptor (IL‐15Rα). Further investigation showed that IL‐15Rα+ TAMs reduced the protein levels of chemokine CX3C chemokine ligand 1 (CX3CL1) in tumor cells to inhibit the recruitment of CD8+ T cells by releasing the IL‐15/IL‐15Rα complex (IL‐15Rc). Administration of an IL‐15Rc blocking peptide markedly suppressed breast tumor growth and overcame the resistance of cancer cells to anti‐ programmed cell death protein 1 (PD‐1) antibody immunotherapy. Interestingly, Granulocyte‐macrophage colony‐stimulating factor (GMCSF) induced γ chain (γc) expression to promote tumor cell‐macrophage crosstalk, which facilitated tumor resistance to IL‐15. Additionally, we observed that the non‐transcriptional regulatory function of hypoxia inducible factor‐1alpha (HIF‐1α) was essential for IL‐15Rc to regulate CX3CL1 expression in tumor cells.
Conclusions
The IL‐15Rc‐HIF‐1α‐CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the tumor microenvironment of breast cancer. Targeting this pathway may provide a potential therapeutic strategy for enhancing the efficacy of cancer immunotherapy.
The worldwide elderly population is on the rise, and aging is a major osteoporosis risk factor. Senescent cells accumulation can have a detrimental effect the body as we age. The ...senescence-associated secretory phenotype (SASP), an essential cellular senescence hallmark, is an important mechanism connecting cellular senescence to osteoporosis. This review describes in detail the characteristics of SASPs and their regulatory agencies, and shed fresh light on how SASPs from different senescent cells contribute to osteoporosis development. Furthermore, we summarized various innovative therapy techniques that target SASPs to lower the burden of osteoporosis in the elderly and discussed the potential challenges of SASPs-based therapy for osteoporosis as a new clinical trial.
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