pH Switchable Nanozyme Platform for Healing Skin Tumor Wound Infected with Drug‐Resistant Bacteria

Abstract

Nanozymes capable of generating reactive oxygen species have recently emerged as promising treatments for wounds infected with drug‐resistant bacteria, possessing a reduced possibility of inducing resistance. However, the therapeutic effect is limited by a shortage of endogenous oxy‐substrates and undesirable off‐target biotoxicity. Herein, a ferrocenyl coordination polymer (FeCP) nanozyme, featuring pH switchable peroxidase (POD)‐ and catalase (CAT)‐like activity is incorporated with indocyanine green (ICG) and calcium peroxide (CaO2) to fabricate an H2O2/O2 self‐supplying system (FeCP/ICG@CaO2) for precise treatment of bacterial infections. At the wound site, CaO2 reacts with water to generate H2O2 and O2. Acting as a POD mimic under an acidic bacterial microenvironment, FeCP catalyzes H2O2 into hydroxyl radicals to prevent infection. However, FeCP switches to CAT‐like activity in neutral tissue, decomposing H2O2 into H2O and O2 to prevent oxidative damage and facilitate wound healing. Additionally, FeCP/ICG@CaO2 shows photothermal therapy capability, as ICG can emit heat under near‐infrared laser irradiation. This heat assists FeCP in fully exerting its enzyme‐like activity. Thus, this system achieves an antibacterial efficiency of 99.8% in vitro for drug‐resistant bacteria, and effectively overcomes the main limitations of nanozyme‐based treatment assays, resulting in satisfactory therapeutic effects in repairing normal and special skin tumor wounds infected with drug‐resistant bacteria.

Advanced nanozymes possess peroxidase-like catalytic activities in biomedical and antibacterial fields: review and progress

“…However, unlike traditional PTT, which requires temperatures exceeding 55 °C to effectively eliminate bacteria, photothermal treatment within the nanozyme antibacterial system tends to be milder (below 45 °C). 109 This ensures that the surrounding healthy tissues remain unharmed, albeit resulting in limited direct bactericidal effects. Thus, the relatively low-temperature PTT primarily plays a supplementary role in enhancing the nanozyme's functionality, contributing to the following: (1) direct promotion of ROS production; (2) facilitation of GSH clearance; and (3) increase in bacterial sensitivity to ROS.…”

Intracellular infection-responsive macrophage-targeted nanoparticles for synergistic antibiotic immunotherapy of bacterial infection

“…When the wound was completely healed, the proinflammatory factors decreased. 68 To explore the capability of ox-Dex-Se/Van nanoparticles to promote angiogenesis, CD31 immunohistochemical staining of skin wound on day 8 was carried out (Fig. 6g).…”

Glucose Oxidase and Catalase-Loaded ZnS Nanozymes for Regulating the Local Microenvironment and Promoting Wound Healing in Diabetes

“…19−21 Although the double enzyme combination greatly improves the high glucose microenvironment, it will produce a lower acidic environment, which is still unfavorable for wound repair. 22,23 Therefore, in order to promote the repair of diabetic wounds in an all-around manner, it is particularly important to improve the adverse acidic environment. ZnS has been widely used in biomedical fields due to its advantages of availability, low cost, safety, biocompatibility, pH sensitivity, and antioxidant and antibacterial properties.…”

“…Although the double enzyme combination greatly improves the high glucose microenvironment, it will produce a lower acidic environment, which is still unfavorable for wound repair. , Therefore, in order to promote the repair of diabetic wounds in an all-around manner, it is particularly important to improve the adverse acidic environment. ZnS has been widely used in biomedical fields due to its advantages of availability, low cost, safety, biocompatibility, pH sensitivity, and antioxidant and antibacterial properties. − It can not only consume H + to improve the acidic environment but also act as a H 2 S donor to release zinc gluconate and H 2 S in the acidic pathological microenvironment, thereby promoting the proliferation, migration, and angiogenesis of fibroblasts (L929) and endothelial cells (ECs). − Zinc gluconate and H 2 S can improve the hyperglycemia environment, promote cell proliferation, promote angiogenesis, and promote wound healing. − Therefore, the combination of GOX, CAT, and ZnS will be conducive to the realization of microenvironment-responsive diabetic skin repair.…”