Nitric Oxide-Releasing Topological Supramolecular Nanocarriers with sliding CD units against MRSA

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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 ationic 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 via sliding CD units into therapeutic polymeric systems is a general design to enhance the healing of several diseases.

Schematic illustration of the NO-releasing topological supramolecular nanocarrier. The sliding and rotating motions of the multiple rings modified with cationic dendrimer and NONOate in the polyrotaxane structure allow the nanocarrier to optimize their molecular conformations to anchor onto the bacterial membrane, defined as self-optimized cooperative multiple-point anchoring, which accelerates and strengthen the interactions between the carrier and microbial, hence enhancing the antibacterial outcome.

Li et al. (2023) Enhanced Bacterial-Infected Wound Healing by Nitric Oxide-Releasing Topological Supramolecular Nanocarriers with Self-Optimized Cooperative Multi-Point Anchoring. Adv. Sci. 2206959.

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