Enhanced Bacterial‐Infected Wound Healing by Nitric Oxide‐Releasing Topological Supramolecular Nanocarriers with Self‐Optimized Cooperative Multi‐Point Anchoring

Abstract

Polymeric systems that provide cationic charges or biocide-release therapeutics are used to treat the bacteria-infected wound. However, most antibacterial polymers based on topologies with restricted molecular dynamics still do not satisfy the clinical requirements due to their limited antibacterial efficacy at safe concentrations in vivo. Here a NO-releasing topological supramolecular nanocarrier with rotatable and slidable molecular entities is reported to provide conformational freedom to promote the interactions between the carrier and the pathogenic microbes, hence greatly improving the antibacterial performance. With improved contacting-killing and efficient delivery of NO biocide from the molecularly dynamic cationic ligand design, the NO-loaded topological nanocarrier achieves excellent antibacterial and anti-biofilm effects via destroying the bacterial membrane and DNA. MRSA-infected rat model is also brought out to demonstrate its wound-healing effect with neglectable toxicity in vivo. Introducing flexible molecular motions into therapeutic polymeric systems is a general design to enhance the healing of a range of diseases. IntroductionBacterial infections are affecting thousands of millions of people, which have been a severe global issue. [1] In recent years,

Macrocycle-Based Antibacterial Materials

“…Briefly, for UiO-66-loaded peroxidase-like activity palladium (Pd) nanozyme for catalyzing hydrogen peroxide to generate ROS, β-CD-HA served as both carriers for the NO donor sodium nitroprusside and UV-triggered switching for regulating Pd–substrate contacts. Zhang, Lin, Ma, and co-workers employed the dendritic poly­(amidoamine)-functionalized β-CDs to fabricate a NO-releasing supramolecular nanocarrier with rotating and sliding molecular motions for killing bacteria and accelerating the healing of infected wounds, accompanied by the synergistic effect of movable cationic rings, multipoint anchoring onto the membrane, and efficient delivery of NO (Figure a) . These hybrid antibacterial platforms demonstrated promising supramolecular macrocycle-based antibacterial materials for wound sterilization and healing.…”

“…(a) A NO-releasing supramolecular nanocarrier with rotating and sliding molecular motions for eliminating bacteria and accelerating infected wound healing. Reproduced with permission under a Creative Commons Attribution-ShareAlike 4.0 International Public License from ref . Copyright 2023 John Wiley and Sons.…”

Enhanced Chemoradiotherapy for MRSA‐Infected Osteomyelitis Using Immunomodulatory Polymer‐Reinforced Nanotherapeutics

“…NO molecules can function as bactericidal agents that can kill bacteria via lipid peroxidation, DNA cleavage, and protein dysfunction, thereby promoting the dissociation of biofilms. [56,57] Meanwhile, NO can also react with O 2 −• to produce more lethal ONOO − molecules, thereby further accelerating the death of bacteria and efficiently eradicating biofilms. Therefore, the aforementioned results revealed the synergistic effect of SNP nanoradiosensitizers and enhanced the performance of chemoradiotherapy in eradicating biofilms.…”

Bacteria‐Targeted Combined with Photothermal/NO Nanoparticles for the Treatment and Diagnosis of MRSA Infection In Vivo

“…The damage of the bacterial membrane prompts more NO to penetrate into the bacterial cell, and then NO reacted with DNA by nitrosation inducing bacterial death. [41] To prove it, the terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay was performed to evaluate the DNA damage after different treatments. As presented in Figure 6c, the TUNEL image of the NIR+B@MPDA-Mal group showed strong green fluorescence, suggesting the fragmentation of DNA.…”