Treatment of Wound Infections in a Mouse Model Using Zn²⁺-Releasing Phage Bound to Gold Nanorods

Abstract

Infections caused by drug-resistant bacteria, particularly Gram-negative organisms, are increasingly difficult to treat using antibiotics. A potential alternative is “phage therapy”, in which phages infect and lyse the bacterial host. However, phage therapy poses serious drawbacks and safety concerns, such as the risk of genetic transduction of antibiotic resistance genes, inconsistent pharmacokinetics, and unknown evolutionary potential. In contrast, metallic nanoparticles possess precise, tunable properties, including efficient conversion of electronic excitation into heat. In this work, we demonstrate that engineered phage-nanomaterial conjugates that target the Gram-negative pathogen Pseudomonas aeruginosa are highly effective as a treatment of infected wounds in mice. Photothermal heating, performed as a single treatment (15 min) or as two treatments on consecutive days, rapidly reduced the bacterial load and released Zn 2+ to promote wound healing. The phage-nanomaterial treatment was significantly more effective than systemic standard-of-care antibiotics, with a >10× greater reduction in bacterial load and ∼3× faster healing as measured by wound size reduction when compared to fluoroquinolone treatment. Notably, the phage-nanomaterial was also effective against a P. aeruginosa strain resistant to polymyxins, a last-line antibiotic therapy. Unlike these antibiotics, the phage-nanomaterial showed no detectable toxicity or systemic effects in mice, consistent with the short duration and localized nature of phage-nanomaterial treatment. Our results demonstrate that phage therapy controlled by inorganic nanomaterials can be a safe and effective antimicrobial strategy in vivo.

Nanosized Shikonin-Fe(III) Coordination Material for Synergistic Wound Treatment: An Initial Explorative Study

“…This was consistent with the topical application and washout of the bioconjugates during treatment and in accordance with previous studies for nanomaterial biodistribution with topical wound healing applications. 42 Inflammatory Condition During the Healing Process. To better elucidate the anti-inflammatory properties of the Shik-Fe NPs in vivo, immunofluorescence staining and routine blood test were carried out on all four treatment groups.…”

“…In addition, compared with specific bacterial cell killing with targeting materials, , Shik-Fe NPs may lack the targeting specificity to given bacterial cells; thus, biosafety assessment is required. Figures S15–S17 evaluated the biosafety of Shik-Fe NPs, confirming that Shik-Fe was very safe and did not cause significant toxicity to the living animals.…”

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

“…In addition, theoretical considerations indicate that phage relaxivity should increase at lower fields (due to slowing down of molecular tumbling), which could also contribute to enhancing contrast at clinically-relevant field strengths (e.g., 1.5 Tesla), albeit with a tradeoff in overall signal intensity. In summary, as a phage-based molecular probe for visualizing targeted bacterial strains with MRI, we envision a synergy in the development of DP1-phage technology with rapidly evolving advances in emerging biotherapeutic platforms involving the use of live microorganisms as well as bacteriophage formulations for noninvasive diagnostics and treatment of diseases like cancer [46][47][48][49][50][51][52] , inflammatory conditions 53,54 , metabolic disorders 55,56 , and antibioticresistant infections [57][58][59][60][61] .…”

Metal and Metal Oxide Nanomaterials for Fighting Planktonic Bacteria and Biofilms: A Review Emphasizing on Mechanistic Aspects

“…In addition, ZnO nanomaterials can also exert antibacterial properties through contact adsorption mechanism and metal ion dissolution mechanism. They all act by zinc ions derived from the degraded of ZnO nanomaterials in an acidic environment [ 45 ]. Zinc ions cause membrane potential disruption by adhering to the cell membrane.…”