Enzyme-Like Photocatalytic Octahedral Rh/Ag2MoO4 Accelerates Diabetic Wound Healing by Photo-Eradication of Pathogen and Relieving Wound Hypoxia.

The harsh environment of diabetic wounds, including bacterial infection and wound hypoxia, is not conducive to wound healing. Herein, an enzyme-like photocatalytic octahedral Rh/Ag2MoO4 is developed to manage diabetic-infected wounds. The introduction of Rh nanoparticles with catalase-like catalytic activity can enhance the photothermal conversion and photocatalytic performance of Rh/Ag2MoO4 by improving near-infrared absorbance and promoting the separation of electron-hole pairs, respectively. Rh/Ag2MoO4 can effectively eliminate pathogens through a combination of photothermal and photocatalytic antibacterial therapy. After bacteria inactivation, Rh/Ag2MoO4 can catalyze hydrogen peroxide to produce oxygen to alleviate the hypoxic environment of diabetic wounds. The in vivo treatment effect demonstrated the excellent therapeutic performance of Rh/Ag2MoO4 on diabetic infected wounds by removing infectious pathogens and relieving oxygen deficiency, confirming the potential application of Rh/Ag2MoO4 in the treatment of diabetic infected wounds.

Stimuli-Actuated Turn-On Theranostic Nanoplatforms for Imaging-Guided Antibacterial Treatment.

Antibacterial theranostic nanoplatforms, which integrate diagnostic and therapeutic properties, exhibit gigantic application prospects in precision medicine. However, traditional theranostic nanoplatforms usually present an always-on signal output, which leads to poor specificity or selectivity in the treatment of bacterial infections. To address this challenge, stimuli-actuated turn-on nanoplatforms are developed for simultaneous activation of diagnostic signals (e.g., fluorescent, photoacoustic, magnetic signals) and initiation of antibacterial treatment. Specifically, by combining the infection microenvironment-responsive activation of visual signals and antibacterial activity, these theranostic nanoplatforms exert both higher accurate diagnosis rates and more effective treatment effects. In this review, the imaging and treatment strategies that are commonly used in the clinic are first briefly introduced. Next, the recent progress of stimuli-actuated turn-on theranostic nanoplatforms for treating bacterial infectious diseases is summarized in detail. Finally, current bottlenecks and future opportunities of antibacterial theranostic nanoplatforms are also outlined and discussed.

Type I photodynamic antimicrobial therapy: Principles, progress, and future perspectives.

The emergence of drug-resistant bacteria has significantly diminished the efficacy of existing antibiotics in the treatment of bacterial infections. Consequently, the need for finding a strategy capable of effectively combating bacterial infections has become increasingly urgent. Photodynamic therapy (PDT) is considered one of the most promising emerging antibacterial strategies due to its non-invasiveness, low adverse effect, and the fact that it does not lead to the development of drug resistance. However, bacteria at the infection sites often exist in the form of biofilm instead of the planktonic form, resulting in a hypoxic microenvironment. This phenomenon compromises the treatment outcome of oxygen-dependent type-II PDT. Compared to type-II PDT, type-I PDT is not constrained by the oxygen concentration in the infected tissues. Therefore, in the treatment of bacterial infections, type-I PDT exhibits significant advantages over type-II PDT. In this review, we first introduce the fundamental principles of type-I PDT in details, including its physicochemical properties and how it generates reactive oxygen species (ROS). Next, we explore several specific antimicrobial mechanisms utilized by type-I PDT and summarize the recent applications of type-I PDT in antimicrobial treatment. Finally, the limitations and future development directions of type-I photosensitizers are discussed. STATEMENT OF SIGNIFICANCE: The misuse and overuse of antibiotics have accelerated the development of bacterial resistance. To achieve the effective eradication of resistant bacteria, pathfinders have devised various treatment strategies. Among these strategies, type I photodynamic therapy has garnered considerable attention owing to its non-oxygen dependence. The utilization of non-oxygen-dependent photodynamic therapy not only enables the effective elimination of drug-resistant bacteria but also facilitates the successful eradication of hypoxic biofilms, which exhibits promising prospects for treating biofilm-associated infections. Based on the current research status, we anticipate that the novel type I photodynamic therapy agent can surmount the biofilm barrier, enabling efficient treatment of hypoxic biofilm infections.

Nitric Oxide-Assisted Photodynamic Therapy for Enhanced Penetration and Hypoxic Bacterial Biofilm Elimination.

The presence of a biofilm matrix barrier and hypoxic microenvironment within the biofilm significantly impedes the efficacy of photodynamic therapy for bacterial biofilm infections. Herein, a phototherapeutic nanoagent with type-I photodynamic behavior and nitric oxide (NO) release performance is reported for overcoming biofilm-associated infectious diseases. Sodium nitroprusside (SNP), a NO donor, is loaded onto amino-modified mesoporous silica nanoparticles (MSN) to form MSN@SNP NPs. The resulting nanoparticles are further modified with a porphyrin-based metal-organic framework (Ti-TCPP MOF) to obtain MSN@MOF/SNP NPs (MMS NPs) for phototherapeutic applications. In the hypoxia biofilm microenvironment, the MMS NPs release NO to enhance the biofilm permeability and induce the generation of hydroxyl radical (•OH) and superoxide anion radical (O2 •- ) via Type-I photodynamic pathway under laser irradiation. Subsequently, the biofilm-associated infections are effectively eliminated through reactive oxygen species (ROS) and NO gas synergistic therapy. In addition, NO also stimulates collagen deposition and promotes angiogenesis in vivo. Therefore, the MMS NPs efficiently treat biofilm-related infections, providing an alternative approach to combat biofilm-associated infectious diseases.

Recent progress in nanozymes for the treatment of diabetic wounds.

The slow healing of diabetic wounds has seriously affected human health. Meanwhile, the open wounds are susceptible to bacterial infection. Clinical therapeutic methods such as antibiotic therapy, insulin treatment, and surgical debridement have made great achievements in the treatment of diabetic wounds. However, drug-resistant bacteria will develop after long-term use of antibiotics, resulting in decreased efficacy. To improve the therapeutic effect, increasing drug concentration is a common strategy in clinical practice, but it also brings serious side effects. In addition, hyperglycemia control or surgical debridement can easily bring negative effects to patients, such as hypoglycemia or damage of normal tissue. Therefore, it is essential to develop novel therapeutic strategies to effectively promote diabetic wound healing. In recent years, nanozyme-based diabetic wound therapeutic systems have received extensive attention because they possess the advantages of nanomaterials and natural enzymes. For example, nanozymes have the advantages of a small size and a high surface area to volume ratio, which can enhance the tissue penetration of nanozymes and increase the reactive active sites. Moreover, compared with natural enzymes, nanozymes have more stable catalytic activity, lower production cost, and stronger operability. In this review, we first reviewed the basic characteristics of diabetic wounds and then elaborated on the catalytic mechanism and action principle of different types of nanozymes in diabetic wounds from three aspects: controlling bacterial infection, controlling hyperglycemia, and relieving inflammation. Finally, the challenges, prospects and future implementation of nanozymes for diabetic wound healing are outlined.