With the increased prevalence of antibiotic-resistant bacteria infections, there is a pressed need for innovative antimicrobial agent. Here, we report a benign ε-polylysine/silver nanoparticle nanocomposite (EPL-g-butyl@AgNPs) with polyvalent and synergistic antibacterial effects. EPL-g-butyl@AgNPs exhibited good stability in aqueous solution and effective antibacterial activity against both Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) bacteria without emergence of bacterial resistance. Importantly, the nanocomposites eradicated the antibiotic-resistant bacteria without toxicity to mammalian cells. Analysis of the antibacterial mechanism confirmed that the nanocomposites adhered to the bacterial surface, irreversibly disrupted the membrane structure of the bacteria, subsequently penetrated cells, and effectively inhibited protein activity, which ultimately led to bacteria apoptosis. Notably, the nanocomposites modulated the relative level of CD3 T cells and CD68 macrophages and effectively promoted infected wound healing in diabetic rats. This work improves our understanding of the antibacterial mechanism of AgNPs-based nanocomposites and offers guidance to activity prediction and rational design of effective antimicrobial nanoparticles.
The chronic infections by pathogenic Pseudomonas aeruginosa (P. aeruginosa) remain to be properly addressed. In particular, for drug‐resistant strains, limited medication is available. An in vivo pneumonia model induced by a clinically isolated aminoglycoside resistant strain of P. aeruginosa is developed. Tobramycin clinically treating P. aeruginosa infections is found to be ineffective to inhibit or eliminate this drug‐resistant strain. Here, a newly developed non‐antibiotics based nanoformulation plus near‐infrared (NIR) photothermal treatment shows a remarkable antibacterial efficacy in treating this drug‐resistant pneumonia. The novel formulation contains 50–100 nm long nanorods decorated with two types of glycomimetic polymers to specifically block bacterial LecA and LecB lectins, respectively, which are essential for bacterial biofilm development. Such a 3D display of heteromultivalent glycomimetics on a large scale is inspired by the natural strengthening mechanism for the carbohydrate–lectin interaction that occurs when bacteria initially infects the host. This novel formulation shows the most efficient bacteria inhabitation and killing against P. aeruginosa infection, through lectin blocking and the near‐infrared‐light‐induced photothermal effect of gold nanorods, respectively. Collectively, the novel biomimetic design combined with the photothermal killing capability is expected to be an alternative treatment strategy against the ever‐threatening drug‐resistant infectious diseases when known antibiotics have failed.
Biofilm is closely related to chronic infections and is difficult to eradicate. Development of effective therapy strategies to control biofilm infection is still challenging. Aiming at biofilm architecture, we designed and prepared near-infrared-activated thermosensitive liposomes with photothermal and antibiotic synergistic therapy capacity to eliminate Pseudomonas aeruginosa biofilm. The liposomes with positive charge and small size aided to enter the biofilm microchannels and locally released antibiotics in infection site. The liposomes could remain stable at 37 °C and release about 80% antibiotics over 45 °C. The biofilm dispersion rate was up to 80%, which was a 7- to 8-fold rise compared to excess antibiotic alone, indicating that the localized antibiotic release and photothermal co-therapy improved the antimicrobial efficiency. In vivo drug-loaded liposomes in treating P. aeruginosa-induced abscess exhibited an outstanding therapeutic effect. Furthermore, photothermal treatment could stimulate the expression of bcl2-associated athanogene 3 to prevent normal tissue from thermal damage. The near-infrared-activated nanoparticle carriers had the tremendous therapeutic potential to dramatically enhance the efficacy of antibiotics through thermos-triggered drug release and photothermal therapy.
The emergence of antibiotic-resistant bacterial strains has made conventional antibiotic therapies less efficient. The development of a novel nanoantibiotic approach for efficiently ablating such bacterial infections is becoming crucial. Herein, a collection of poly(5-(2-ethyl acrylate)-4-methylthiazole-g-butyl)/copper sulfide nanoclusters (PATA-C4@CuS) was synthesized for efficient capture and effective ablation of levofloxacin-resistant Gram-negative and Gram-positive bacteria upon tissue-penetrable near-infrared (NIR) laser irradiation. In this work, we took advantage of the excellent photothermal and photodynamic properties of copper sulfide nanoparticles (CuSNPs) upon NIR laser irradiation and thiazole derivative as a membrane-targeting cationic ligand toward bacteria. The conjugated nanoclusters could anchor the bacteria to trigger the bacterial aggregation quickly and efficiently kill them. These conjugated nanoclusters could significantly inhibit levofloxacin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus amyloliquefaciens at 5.5 μg/mL under NIR laser irradiation (980 nm, 1.5 W cm, 5 min), which suggested that the heat and reactive oxygen species (ROS) generated from the irradiated CuSNPs attached to bacteria were effective in eliminating and preventing the regrowth of the bacteria. Importantly, the conjugated nanoclusters could promote healing in bacteria-infected rat wounds without nonspecific damage to normal tissue. These findings highlight the promise of the highly versatile multifunctional nanoantibiotics in bacterial infection.
Patients with diabetic wounds have deficient local and systemic cellular immunity. Herein, a new silver nanoparticle-containing hydrogel with antifouling properties was developed for enhancing the immune response in diabetic wound healing. The antifouling property was obtained by adjusting the composition of cationic chitosan and anionic dextran to approach zero charge. Furthermore, this hybrid hydrogel showed long-lasting and broad-spectrum antibacterial activity. Rapid wound contraction was observed after the treatment with the hydrogel, which suggested its superior healing activity to promote fibroblast migration, granulation tissue formation, and angiogenesis. The upregulation of CD68+ and CD3+ expression levels demonstrated that the hydrogel could trigger immune responses in the treatment of wound healing. These results show that this antifouling hybrid hydrogel as a wound dressing provided a promising strategy for the treatment of diabetic ulcers.
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