Engineering Phage Nanocarriers Integrated with Bio-Intelligent Plasmids for Personalized and Tunable Enzyme Delivery to Enhance Chemodynamic Therapy.

Customizable and number-tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4-Lox-DNA-Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron-based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO-Keap1 plasmid (DNA) with tumor hypoxia-activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio-intelligent plasmids, presenting a promising approach for tumor therapy.

Gelatinase-responsive biodegradable targeted microneedle patch for abscess wound treatment of S. aureus infection.

Abscess wound caused by bacterial infection is usually difficult to heal, thus greatly affect people's quality of life. In this study, a biodegradable drug-loaded microneedle patch (MN) is designed for targeted eradication of S. aureus infection and repair of abscess wound. Firstly, the bacterial responsive composite nanoparticle (Ce6@GNP-Van) with a size of about 182.6 nm is constructed by loading the photosensitizer Ce6 into gelatin nanoparticle (GNP) and coupling vancomycin (Van), which can specifically target S. aureus and effectively shield the phototoxicity of photosensitizer during delivery. When Ce6@GNP-Van is targeted and enriched in the infected regions, the gelatinase secreted by the bacteria can degrade GNP in situ and release Ce6, which can kill the bacteria by generating ROS under laser irradiation. In vivo experiments show that the microneedle is basically degraded in 10 min after inserting into skin, and the abscess wound is completely healed within 13 d after applying Ce6@GNP-Van-loaded MN patch to the abscess wound of the bacterial infected mice with laser irradiation, which can simultaneously achieve the eradication of biofilm and subsequent wound healing cascade activation, showing excellent synergistic antibacterial effect. In conclusion, this work establishes a synergistic treatment strategy to facilitate the repair of chronic abscess wound.