Nucleus-Targeting Photosensitizers Enhance Neutrophil Extracellular Traps for Efficient Eradication of Multidrug-Resistant Bacterial Infections.

Neutrophil extracellular traps (NETs) are web-like complexes of DNA and proteins that are extruded by activated neutrophils and play critical roles as major components of the innate immune response against pathogen invasion. However, some microbes have developed strategies to evade NET attacks, leading to impaired immune defenses and persistent infections. In this study, an engineered neutrophil strategy for enhancing the antibacterial activity of NETs is developed.

Light-Activated Nanocatalyst for Precise In-Situ Antimicrobial Synthesis via Photoredox-Catalytic Click Reaction.

The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S.

Exciting Bacteria to a Hypersensitive State for Enhanced Aminoglycoside Therapy by a Rationally Constructed AIE Luminogen.

The diminishing effectiveness of existing aminoglycoside antibiotics (AGs) compels scientists to seek new approaches to enhance the sensitivity of current AGs. Despite ongoing efforts, currently available approaches remain restricted. Herein, a novel strategy involving the rational construction of an aggregation-induced-emission luminogen (AIEgen) is introduced to significantly enhance Gram-positive bacteria's susceptibility to AGs.

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy.

Type-I Photosensitizer-Triggered Controllable Carbon Monoxide Release for Effective Treatment of Staph Skin Infection.

() infection is a major infectious skin disease that is highly resistant to conventional antibiotic treatment and host immune defense, leading to recurrence and exacerbation of bacterial infection. Herein, we developed a photoresponsive carbon monoxide (CO)-releasing nanocomposite by integrating anion-π type-I photosensitizer () and organometallic complex () for the treatment of planktonic and biofilm-associated infections. After optimizing the molar ratio of and , the prepared nanoparticles, , not only ensured sufficient loading of CO donors and efficient CO generation but also showed negligible free ROS leakage under light irradiation, which helped to avoid tissue damage caused by excessive ROS.

Lysosome-Targeting Aggregation-Induced Emission Nanoparticle Enables Adoptive Macrophage Transfer-Based Precise Therapy of Bacterial Infections.

Traditional antibacterial procedures are getting inefficient due to the emergence of antimicrobial resistance, which makes alternative treatments in urgent demand. However, the selectivity toward infectious bacteria is still challenging. Herein, by taking advantage of the self-directed capture of infectious bacteria by macrophages, we developed a strategy to realize precise antibacterial photodynamic therapy (APDT) through adoptive photosensitizer-loaded macrophage transfer.

Recent Organic Photosensitizer Designs for Evoking Proinflammatory Regulated Cell Death in Antitumor Immunotherapy.

In the past decades, immunotherapy has achieved a series of clinical successes in the field of cancer. However, existing therapeutic options usually show a low immune response to solid tumors caused by immunosuppressive "cold" tumor microenvironment (TME). Several types of proinflammatory regulated cell death (RCD), mainly including ferroptosis and pyroptosis, have been studied recently, which can provide proinflammatory signals and immunogenicity necessary for remodeling TME and activating an antitumor immune response.

Customized Multifunctional Peptide Hydrogel Scaffolds for CAR-T-Cell Rapid Proliferation and Solid Tumor Immunotherapy.

CAR-T-cell therapies must be expanded to obtain a large number of effector cells quickly, and the current technology cannot address this challenge. A longer operational time would lose or alter the function and phenotype of CAR-T cells in response to therapy, and it also causes a loss in the optimal treatment time for patients. At present, lower survival time and homing efficiency reduce the antitumor effect of CAR-T in vivo.

Near-infrared chemiluminescent nanoprobes for deep imaging and synergistic photothermal-nitric-oxide therapy of bacterial infection.

Bacterial infection is the leading cause of many serious inflammation diseases threatening human health. Existing theranostic options for bacterial infection are always complicated and unsatisfactory. There is an increasing interest in developing a more effective theranostic approach for the treatment of infections.

From main-chain conjugated polymer photosensitizer to hyperbranched polymer photosensitizer: expansion of the polymerization-enhanced photosensitization effect for photodynamic therapy.

Three conjugated polymers that have the same donor-acceptor structure but totally different architectures are designed to show both Type-I and Type-II photosensitization abilities simultaneously, among which the hyperbranched polymer shows the best performance in both and experiments, superior to even the commonly used clinical photosensitizer of hemoporfin.

A Nuclear-Targeted AIE Photosensitizer for Enzyme Inhibition and Photosensitization in Cancer Cell Ablation.

The nucleus is considered the ideal target for anti-tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear-targeted material MeTPAE with aggregation-induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton.

A Polarity-Sensitive Ratiometric Fluorescence Probe for Monitoring Changes in Lipid Droplets and Nucleus during Ferroptosis.

Ferroptosis regulates cell death through reactive oxygen species (ROS)-associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of an LD/nucleus dual-targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor-acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations.

AIEgen-coupled upconversion nanoparticles eradicate solid tumors through dual-mode ROS activation.

Reactive oxygen species (ROS) are essential for the regulation of antitumor immune responses, where they could induce immunogenic cell death, promote antigen presentation, and activate immune cells. Here, we report the development of near-infrared (NIR)-driven immunostimulants, based on coupling upconversion nanoparticles with aggregation-induced emission luminogens (AIEgens), to integrate the immunological effects of ROS for enhanced adaptive antitumor immune responses. Intratumorally injected AIEgen-upconversion nanoparticles produce high-dose ROS under high-power NIR irradiation, which induces immunogenic cell death and antigen release.

Bio-orthogonal click reaction-enabled highly specific in situ cellularization of tissue engineering scaffolds.

Tissue engineering generally utilizes natural or synthetic scaffolds to repair or replace damaged tissues. However, due to the lack of guidance of biological signals, most of the implanted scaffolds have always suffered from poor in vivo cellularization. Herein, we demonstrate a bio-orthogonal reaction-based strategy to realize in situ specific and fast cellularization of tissue engineering scaffold.

Visualization and In Situ Ablation of Intracellular Bacterial Pathogens through Metabolic Labeling.

Protected by the host cells, the hidden intracellular bacteria are typically difficult to kill by common antibiotics and cannot be visualized without complex cellular pretreatments. Herein, we successfully developed a bacteria-metabolizable dual-functional probe TPEPy-d-Ala, which is based on d-alanine and a photosensitizer with aggregation-induced emission for fluorescence turn-on imaging of intracellular bacteria in living host cells and photodynamic ablation in situ. Once metabolically incorporated into bacterial peptidoglycan, the intramolecular motions of TPEPy-d-Ala are inhibited, leading to an enhanced fluorescent signal, which allows the clear visualization of the intracellular bacteria.

Specific Targeting, Imaging, and Ablation of Tumor-Associated Macrophages by Theranostic Mannose-AIEgen Conjugates.

Tumor-associated macrophages (TAMs) that exist in tumor microenvironment promote tumor progression and have been suggested as a promising therapeutic target for cancer therapy in preclinical studies. Development of theranostic systems capable of specific targeting, imaging, and ablation of TAMs will offer clinical benefits. Here we constructed a theranostic probe, namely, TPE-Man, by attaching mannose moieties to a red-emissive and AIE (aggregation-induced emission)-active photosensitizer.

Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I.

Bioactive peptides derived from proteins generally need to be folded into secondary structures to activate downstream signaling pathways. However, synthetic peptides typically form random-coils, thus losing their bioactivities. Here, we show that by introducing a self-assembling peptide motif and using different preparation pathways, a peptide from insulin-like growth factor-I (IGF-1) can be folded into an α-helix and β-sheet.

Seeing the fate and mechanism of stem cells in treatment of ionizing radiation-induced injury using highly near-infrared emissive AIE dots.

Ionizing radiation-induced skin injury is a common and severe side effect of radiotherapy suffered by cancer patients. Although the therapy using stem cells has been demonstrated to be effective, fully grasping their role in the repair of radiation-induced skin damage remains challenging owing to the lack of highly reliable cell trackers. Herein, we report the design and synthesis of a highly near-infrared emissive organic nanodots with aggregation-induced emission (AIE) characteristic, which give excellent performance in seeing the fate and regenerative mechanism of adipose-derived stem cells (ADSCs) in treatment of radiation-induced skin injury.

Multifunctional Liposome: A Bright AIEgen-Lipid Conjugate with Strong Photosensitization.

Liposomes have been used as popular drug delivery systems for cancer therapy. However, it is difficult to track traditional liposome delivery systems in an efficient and stable fashion to assess their delivery efficacy and biodistribution after administration. Meanwhile, conventional fluorescent liposomes containing optical tracers face the challenge of aggregation-caused quenching.

A Light-Up Probe with Aggregation-Induced Emission for Real-Time Bio-orthogonal Tumor Labeling and Image-Guided Photodynamic Therapy.

Bio-orthogonal tumor labeling is more effective in delivering imaging agents or drugs to a tumor site than active targeting strategy owing to covalent ligation. However, to date, tumor-specific imaging through bio-orthogonal labeling largely relies on body clearance to differentiate target from the intrinsic probe signal owing to the lack of light-up probes for in vivo bio-orthogonal labeling. Now the first light-up probe based on a fluorogen with aggregation-induced emission for in vivo bio-orthogonal fluorescence turn-on tumor labeling is presented.

Dual-Responsive Metabolic Precursor and Light-Up AIEgen for Cancer Cell Bio-orthogonal Labeling and Precise Ablation.

Metabolic glycoengineering of unnatural glycans with bio-orthogonal chemical groups and a subsequent click reaction with fluorescent probes have been widely used in monitoring various bioprocesses. Herein, we developed a dual-responsive metabolic precursor that could specifically generate unnatural glycans with azide groups on the membrane of targeted cancer cells with high selectivity. Moreover, a water-soluble fluorescent light-up probe with aggregation-induced emission (AIE) was synthesized, which turned its fluorescence on upon a click reaction with azide groups on the cancer cell surface, enabling special cancer cell imaging with low background signal.

Polymeric nanorods with aggregation-induced emission characteristics for enhanced cancer targeting and imaging.

Polymeric nanorods loaded with AIEgens are synthesized via nano-precipitation under ultrasound sonication, where prolonged sonication time could induce a nanodot-to-nanorod transition. These AIE nanorods, but not the nanodots, could be selectively internalized into cancer cells, which show better tumor accumulation, higher tumor penetration and more efficient in vivo cancer cell uptake.

Metal-Organic-Framework-Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy.

Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL-100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3-azido-d-alanine (d-AzAla).