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.

Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic antibacterial therapy has been widely studied due to its low induction of resistance. However, photosensitizers that can efficiently generate reactive oxygen species (ROS) through both type I and type II mechanisms and that have the capability of multiple modes of action are rarely reported. Addressing this issue, we developed a near-infrared-emitting triphenylamine indole iodoethane (TTII) and its silver(I) self-assembled (TTIIS) aggregation-induced emission (AIE) photosensitizer for multimode bacterial infection therapy. TTII can efficiently produce both Type I ROS •OH and Type II ROS 1O2. Interestingly, the Ag(I)-π interaction contributed in TTIIS efficiency promotion of the generation of 1O2. Moreover, by releasing Ag+, TTIIS enabled photodynamic-Ag(I) dual-mode sterilization. As a result, TTIIS achieved an effective enhancement of antibacterial activity, with a 1-2-fold boost against multidrug-resistant Escherichia coli (MDR E. coli). Both TTII and TTIIS at a concentration as low as 0.55 μg mL-1 can kill more than 98% of methicillin resistant Staphylococcus aureus (MRSA) on MRSA-infected full-thickness defect wounds of a mouse, and both TTII and TTIIS were effective in eliminating the bacteria and promoting wound healing.

Bacterial infection has been regarded as a life-threatening problem in clinic. In addition to screening of new antibiotics, it is important to develop highly effective antibacterial materials against antibiotic resistance with capacities on modulating chronic inflammation. Herein, aligned Chlorin e6 (Ce6) conjugated silk fibroin electrospun fibers were successfully fabricated on silk fibroin based film via electrospining to achieve effective photodynamic antibacterial activities under near infrared (NIR) irradiation. The aligned electrospun fiber based film composite (SFCF@Film) exhibited good mechanical properties and desirable hemocompatibility. SFCF@Film provided a promising guidance cue for directing cell orientation and promoting cell growth. Significantly, SFCF@Film effectively generated ROS under NIR irradiation to kill S. aureus for treating wound infections within 10 min and promoted M2 polarization of macrophages for wound healing at later stage. Therefore, we believed that this engineered bioscaffold can be a powerful strategy for handling wound infection.

Dental caries represents one of the most prevalent diseases worldwide, characteristic of the growth of dental plaque and demineralization of tooth enamel. Current medications for eradication of dental plaques and prevention of demineralization suffer from several limitations to overcome, calling for novel strategies with great potency in eliminating cariogenic bacteria and dental plaque that forms, as well as in inhibiting the demineralization of enamel, into an integrated system. Considering the potency of photodynamic therapy in bacteria inactivation and the composition of enamel, we herein report that the novel photodynamic nano hydroxyapatite (nHAP), named Ce6 @QCS/nHAP, was useful for this purpose. Ce6 @QCS/nHAP, comprised of quaternary chitosan (QCS)-coated nHAP loaded with chlorin e6 (Ce6), exhibited good biocompatibility and non-compromised photodynamic activity. In vitro studies revealed that Ce6 @QCS/nHAP could effectively associate with cariogenic Streptococcus mutans (S. mutans), leading to a significant antibacterial effect through photodynamic killing and physical inactivation against the planktonic microbe. Three-dimensional fluorescence imaging suggested that Ce6 @QCS/nHAP exhibited a superior S. mutans biofilm penetration capacity to free Ce6, resulting in effective dental plaque eradiation when light irradiation was applied. The number of surviving bacteria in biofilm was at least 2.8 log units lower in the Ce6 @QCS/nHAP group compared to that in the free Ce6 group. Further, in the S. mutans biofilm-infected artificial tooth model, treatment with Ce6 @QCS/nHAP also resulted in the significant prevention of hydroxyapatite disks from demineralization, with lower percentage of fragmentation and weight loss These data suggest that our photodynamic nanosystem can effectively eradicate dental plaque while also significantly protecting artificial tooth from demineralization, opening up new possibilities in treating bacterium-associated dental caries.

The emergence of multidrug-resistant (MDR) bacteria has made wound infection treatment difficult, calling for novel strategies for effective elimination of bacteria in wounds and promoting their recovery. Herein, we report a novel chitosan antibacterial sponge combining zinc oxide particles (ZnO) and the photosensitizer chlorin e6 (Ce6), named CS-ZnO/Ce6 sponge for combating multidrug-resistant bacteria and treating skin abscesses. The fabricated CS-ZnO/Ce6 sponge had porous structure with high porosity, conducive to absorbing the wound exudate. Meanwhile, the hemostatic property of this sponge enabled it to stop the continuous bleeding of the wound. Upon 660 nm light irradiation, the CS-ZnO/Ce6 sponge exhibited an instant photodynamic bactericidal effect against several typical MDR strains, and the presence of ZnO could continuously inhibit bacterial growth. In addition, local remedy of methicillin-resistant Staphylococcus aureus (MRSA)-infected mice with CS-ZnO/Ce6 sponge with light irradiation caused a potent immediate bacterial killing effect and prolonged bacteriostasis in mice with skin abscesses, leading to the rapid recovery of the wound. The biocompatibility of the CS-ZnO/Ce6 sponge in mice was also verified by histological examination of the main organs. Collectively, the CS-ZnO/Ce6 sponge with broad-spectrum antibacterial activity and long-term bacterial inhibition potential could be useful for treating microbial infections and accelerating wound healing.

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.

As we step into the post-antibiotic era, the accelerated emergence of antibiotic-resistant pathogenic bacteria poses an increasingly serious threat to public health. The formation of antibiotic-resistant biofilms further challenges currently available drugs and treatment options, calling for novel strategies for effective ablation of such biofilm with minimal concern on safety and development of resistance. Herein, we report a novel type of photodynamic nanoagent, composed of chlorin e6 (Ce6)-loaded water-soluble chitosan-coated iron oxide nanoparticles (named Ce6@WCS-IONP), for drug-resistant bacteria killing and biofilm eradication. The fabricated Ce6@WCS-IONP has negligible toxicity to mammalian cells and exhibited equivalent singlet oxygen generation capacity to free Ce6; however, its association with methicillin-resistant Staphylococcus aureus (MRSA) was greatly enhanced, as evidenced by flow cytometry analysis and transmission electron microscope. In vitro studies verified that Ce6@WCS-IONP has superior photodynamic bactericidal effect against planktonic MRSA. Furthermore, with the aid of the cationic nature and small size, Ce6@WCS-IONP could effectively penetrate into MRSA biofilm, revealed by 3D fluorescence imaging. Both biomass analysis and viable bacteria counting demonstrated that Ce6@WCS-IONP showed potent biofilm ablation efficacy, averagely 7.1 log unit lower than that in free Ce6 group upon identical light irradiation. In addition, local treatment of MRSA-infected mice with Ce6@WCS-IONP plus light irradiation resulted in significant antibacterial and wound healing effect, accompanied by good biocompatibility in vivo. Collectively, photosensitizer-loaded cationic IONP with effective biofilm penetration and photodynamic eradication potential might be a promising nano platform in fighting against antibiotic-resistant microbial pathogen and biofilm.

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.