The rising prevalence of antibiotic-resistant bacteria pathogens has attracted increasing concern in the whole world. The antiadhesion strategy without triggered bacterial resistance is currently considered a promising alternative to treat bacteria-induced infections. Here, we developed a novel bacteria-binding florescent polymeric nanoplatform for nonlethal antiadhesion therapy of bacterial infections. This versatile platform will allow simultaneous bacterial agglutination and fluorescent reporting for both Gram-positive and Gram-negative bacteria by taking advantage of strong interaction between the benzoxaborole groups and diol moieties on bacterial surfaces. Furthermore, impressive performance of inhibiting biofilm formation was entirely shown in the generic cell-binding glues. The trapping nanoparticles were capable of taking invasive bacteria pathogens away from the infected host cells with negligible damage to neither bacterial nor host cells, which will not trigger drug resistance, indicating a far-reaching future of the potential application for antiadhesion therapy of whole-bacterial infection diseases.
Pseudomonas aeruginosa can cause a multitude of inflammations in humans. Due to its ability to form biofilm, the bacteria show durable resistance to drugs. Herein, we developed a heteromultivalent ligand-decorated nanotherapeutic inspired by living system for inhibition of antibiotic-resistant bacterial pneumonia. The nanotherapeutic with a heteromultivalent glycomimetic shell can specifically recognize P. aeruginosa to inhibit its biofilm formation and protect native cells from bacterial infection; the rate of biofilm inhibition was up to 85%. The nanotherapeutic with a bioresponsive hydrophobic core can protonate and control drug release in the microenvironment of bacterial infections. By utilizing these properties, the nanotherapeutics can effectively penetrate the internal structure of biofilms to release the drug, dispersing the biofilm by over 80% under laser irradiation. In vivo bioinspired nanotherapeutics have the potential to efficiently inhibit antibiotic-resistant P. aeruginosa-induced pneumonia. Collectively, we expect biomimicking systems to be the next generation of prevention and treatment as integrated antibacterial agents against P. aeruginosa.
An entirely new strategy is explored for directional transport delivery of antibiotics to bacteria utilizing a bacteria-activated nanoplatform.
Variations in physiological parameters (i.e., pH, redox potential, and ions) for distinct types of diseases make them attractive targets. Ionizable groups capable of pH-dependent charge conversion impart pH-switchable materials under acid condition through the protonation effect, which stimulates the emergence of various pH-inspired materials. However, it is confusing to distinguish preferable groups for high-efficiency drug-delivery vehicles attributing to the lack of perceiving the relationship between protonation and activity. Herein, we developed a series of bioinspired ionizable glycomimetics responses to the ambient variation from physiological environment (pH 7.4) to bacterial infectious acidic microenvironment (pH 6.0) to explore the protonation–activity relationship of various ionizable groups. The nanoparticles are coated with bacterial adhesion molecules galactose and fucose to target Pseudomonas aeruginosa. Moreover, the particle cores were composed of ionizable polymers responding to acidic microenvironment changes and entrapped antibiotic payload. Ionizable glyconanoparticles targeted bacteria and local cues as triggers to transfer payloads in on-demand patterns for the inhibition of bacteria-related infection. Significantly, we find that the nanoparticles with the pH-sensitive block of ionizable poly(2-(diisopropylamino)ethyl methacrylate) (pDPA) exhibit predominant bacterial adhesion and killing and growth inhibition of biofilm in acid environment (pH 6.0) due to the ionizable polymer protonation effect with more positive charge cooperated with the lectin-targeted effect of polysaccharide causing a huge bacterial aggregation and a highly favorable germicidal effect. The nanoparticles with poly(2-(hexamethyleneimino)ethyl methacrylate) (pHMEMA) have suboptimal antibacterial activity but advanced protonation at pH 6.3 compared to pDPA at 6.1, suggesting its selection as an applicable pH-switchable group for a slightly higher acid microenvironment like tumor (pH 6.9–6.5) because of the efficient performance after protonation than at deprotonation. On the other hand, the glycomimetic containing poly(2-(dibutylamino)ethyl methacrylate) (pDBA) as a pH-sensitive moiety displayed weak antimicrobial activity and superior stability before protonation (pH 4.7), which make it possible to prevent premature drug leakage, suggesting that pDBA is a good candidate to be applied to construct pH-sensitive drug-delivery carriers for the treatment of bacteria-related infection with a low acidic microenvironment. Overall, the structure–activity relationship of ionizable glycomimetics for the inhibition of bacteria signifies not only the development of a drug-delivery system but also the mechanism-dependent treatment of nanomedicine for infectious diseases.
The Gram-negative bacteria Pseudomonas aeruginosa is one famous bacterial strain owing to its ability to effectively form biofilms, which is a front-line mechanism of bacterial tolerance. Herein, the near-infrared-induced nanocomposites were one-step prepared by modifying copper sulfide nanoparticle with peptide to effectively eradicate Pseudomonas aeruginosa biofilm through electrostatic interaction, photodynamic effect and photothermal effect. These nanocomposites could rapidly adhere to the surface of bacteria, and irreversible damage the bacterial membrane under near-infrared laser irradiation. Furthermore, the nanocomposites could selectively eliminate bacteria over mammalian cell without distinct toxicity to NIH 3T3 cells. The nanocomposites will exert a far-reaching impact on the future design of biocompatible near-infrared-induced antibacterial agents, exhibiting its potential applications in Gram-negative bacteria and biofilm infections.
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