UNASSIGNED: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.
UNASSIGNED: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme\'s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
UNASSIGNED: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes\' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.
UNASSIGNED: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.

UNASSIGNED: Photodynamic antimicrobial therapy (PDAT) has been extensively studied because of its potential applications such as precise controllability, high spatiotemporal accuracy, and non-invasiveness. More importantly, it is difficult for bacteria to develop resistance to the aforementioned PDATs. However, the selectivity of traditional PDAT methods to bacteria is generally poor, so it has been proposed to introduce positively charged components such as quaternary ammonium salts to enhance the targeting of bacteria; however, they always possess high toxicity to normal cells. As a result, measures should be taken to enhance the targeting of bacteria and avoid side effects on normal cells.
UNASSIGNED: In our work, we creatively design a nanoplatform with high anti-bacterial efficiency, low side effects and its size is approximately 121 nm. BSA, as a nanocarrier, encapsulates the photosensitizer (E)-4-(4-(diphenylamino)styryl)-1-methylpyridin-1-ium with AIE properties named as BSA-Tpy, which increases its circulation time in vivo and improves the biocompatibility. Under acidic conditions (pH = 5.0), the surface positive charge of the BSA-Tpy is increased to +18.8 mV due to protonation of amine residues to achieve the targeting effect on bacteria. Besides, under the irradiation of white light, the BSA-Tpy will produce ROS to kill bacteria efficiently about 99.99% for both Gram-positive and Gram-negative bacteria, which shows the potential application value for the treatment of infected wounds.
UNASSIGNED: We have developed a feasible method for photodynamic antibacterial therapy, possessing excellent biocompatibility and high antibacterial efficiency with good fluorescence imaging property.

The main treatment for bacterial infections is antibiotic therapy, but the emergence of bacterial resistance has severely limited the efficacy of antibiotics. Therefore, another effective means of treating bacterial infections is needed to alleviate the therapeutic pressure caused by antibiotic resistance. Photodynamic antibacterial therapy (PDAT) has gradually entered people\'s field of vision as an infection treatment method that does not depend on antibiotics. PDAT induces photosensitizers (PS) to produce reactive oxygen species (ROS) under light irradiation, and kills bacteria by destroying biological macromolecules at bacterial infection sites. In recent years, researchers have found that some nanomaterials delivering PS can improve PDAT through targeted delivery or synergistic therapeutic effect. Therefore, in this article, we will review the recent applications of several nanomaterials in PDAT, including metal nanoclusters, metal-organic frameworks, and other organic/inorganic nanoparticles, and discuss the advantages and disadvantage of these nanomaterials as carriers for delivery PS to further advance the development of PDAT.

Wound management is a major global issue, and there is a growing challenge to develop more effective hemostatic dressings to control bleeding and prevent pathogen infections. In this study, a multifunctional wound dressing was developed to meet the clinical need. The hemostatic layer of wound dressing can quickly stop the bleeding. Meanwhile, the detection layer is used for real-time fluorescence monitoring of the bacterial colonization. When infection occurs, wound dressing is further subjected to illumination for in-situ photodynamic antibacterial treatment. In the rabbit ear artery hemostasis model, the hemostasis time of the wound dressing was 1 s. The detection limit of the wound dressing was 1.4 × 105 CFU/cm2 for Escherichia coli, 5.9 × 105 CFU/cm2 for Staphylococcus aureus, and 3.8 × 106 CFU/cm2 for Pseudomonas aeruginosa, respectively. Compared with the control group, an enhanced wound closure (up to 97.3%) were observed in mice treated with the wound dressing. In vitro and in vivo experiment results suggested that the wound dressing was effective in killing pathogenic bacterial and exhibited good biological compatibility, and induced no inflammatory reaction. The proposed design prevents massive bleeding and wound infection, and further promotes wound healing. STATEMENT OF SIGNIFICANCE: In this work, we developed a multifunctional wound dressing, capable of rapid hemostasis, colorimetric monitoring of bacterial infection, and in situ photodynamic antibacterial. The hemostatic layer can quickly stop the bleeding due to its large specific surface area and adsorption pore size for platelet at bleeding site. Meanwhile, the detection layer can intelligently monitor the bacterial infection and respond to report bacterial infection by emitting fluorescence. When infection occurs, wound dressing can be used for in-situ photodynamic antibacterial treatment. In vitro and in vivo results showed that the wound dressing was biocompatible, prevented massive bleeding and wound infection, and further promoted wound healing.

The development of alternative strategies for the efficient treatment of subcutaneous abscesses that do not require the massive use of antibiotics and surgical intervention is urgently needed. Herein, a novel synergistic antibacterial strategy based on photodynamic (PDT) and NO gas therapy is reported, in which, a PDT-driven NO controllable generation system (Ce6@Arg-ADP) is developed with l-Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier. This carrier not only displays superior bacterial association and biofilm penetration performance, but also acts as a versatile NO donor. Following efficient penetration into the interior of the biofilms, Ce6@Arg-ADP can rapidly produce massive NO via utilizing the H2 O2 generated during PDT to oxidize Arg-ADP to NO and l-citrulline, without affecting singlet oxygen (1 O2 ) production. The combination of 1 O2 and the reactive by-products of NO offers notable synergistic antibacterial and biofilm eradication effects. Importantly, following efficient elimination of all bacteria from the abscess site, Arg-ADP can further generate trace quantities of NO to facilitate the angiogenesis and epithelialization of the wound tissues, thereby notably promotes wound healing. Together, this study clearly suggests that Arg-ADP is a versatile NO donor, and the combination of PDT and NO represents a promising strategy for the efficient treatment of subcutaneous abscesses.

Pathogenic bacterial infections associated with wound healing progress usually result in serious complications. Herein, biocompatible and antimicrobial electrospun nanofibrous mats with photodynamic therapy (PDT) effect were fabricated to accelerate the infected wound healing. The nanofibrous mats were fabricated by co-electrospining of polyanionic poly(γ-glutamic acid) (γ-PGA) and cationic photosensitizer 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra (p-toluenesulfonate) (TMPyP) in aqueous solution and stabilized by the chemical crosslinking. The as-prepared nanofibrous mats can not only confer the moist microenvironment to the wound bed, but also provide potent bactericidal activity upon visible light irradiation by releasing the cytotoxic reactive oxygen species (ROS). The antibacterial assay in vitro showed that they can effectively eradicate the board-spectrum bacteria at a relatively low loading dose of TMPyP (e.g., 0.1 wt%). Meanwhile, those nanofibrous mats showed good biocompatibility with no obvious adverse effects on mammalian cells and red blood cells (RBCs). The animal test in vivo suggested that the restrained inflammatory reaction and better wound healing could be achieved upon timely and effective antibacterial treatment with negligible local toxicities. This biocompatible and antibacterial γ-PGA-TMPyP nanofibrous mat may show great potential in practical infection-resistant applications, particularly for wound dressing applications.

With the increase of bacterial infections in clinical practice, it becomes a public health problem which has aroused worldwide attention. Fluorescence imaging-guided photodynamic antibiosis has recently emerged as a promising protocol to solve this problem. However, developing a super powerful fluorescent material allowing facile preparation, long emission wavelength, rapid bacterial discrimination, washing-free staining, and high photodynamic antibacterial efficiency in a single entity, is highly desirable but remains challenging. In this study, we utilize for the first time a water-soluble near-infrared (NIR) emissive luminogen with aggregation-induced emission (AIE) characteristics, namely TTVP, for simultaneous dual applications of Gram-positive bacteria discrimination and photodynamic antibiosis. TTVP is able to selectively target Gram-positive bacteria over Gram-negative bacteria through a washing-free procedure after only 3 s incubation period, which is at least 100-fold shorter than those of previously reported protocols, implying ultrafast bacterial discrimination features. Meanwhile, TTVP exhibits extremely high reactive oxygen species generation efficiency, which is far superior to that of most popularly used photosensitizers, representing one of the best candidates for photodynamic antibiosis. In vitro and in vivo results demonstrate that TTVP provides extraordinary performance on photodynamic antibacterial therapy. This study thus offers a blueprint for the next generation of antibacterial materials.