Oxidation of rim sulfur atoms is shown to furnish corannulene-based electron acceptors of high strengths.
Bacterial infection is becoming increasingly lethal with the emergence of antimicrobial resistance, and wounds plagued by such infection are notoriously difficult to heal. Here, the first use of galactose-black phosphorus nanosheets, (Gal-BP NSs) as a delivery platform for synergistic antibiotic (kanamycin, Kana) and photothermal treatments against the Gram-negative microbial strain, Pseudomonas aeruginosa PAO1 (PAO1) is reported. Gal-BP NSs@Kana can actively target PAO1 and release kanamycin into the bacterial cytoplasm upon near-infrared laser irradiation. This strategy kills most of the PAO1 through a simultaneous burst of intracellular kanamycin release and photothermal treatment. Comparable antibacterial activities of Gal-BP NSs@Kana are observed within in vivo mouse models at their wound sites. In addition, this platform accelerates wound healing from PAO1 infection via promotion of neoangiogenesis and collagen production at the wound sites. This work demonstrates the material properties of Gal-BP NS in fighting bacterial infections and in the treatment of wound healing.
Nanoparticles have been widely used in detection and killing of bacteria; however, targeting bacteria is still challenging. Delicate design of nanoparticles is required for simultaneous targeting, detection, and therapeutic functions. Here the use of Au/MnFe2O4 (Au/MFO) Janus nanoparticles to target Gram‐positive bacteria via metabolic labeling is reported and realize integrated self‐reporting and thermal killing of bacteria. In these nanoparticles, the Au component is functionalized with tetrazine to target trans‐cyclooctene group anchored on bacterial cell wall by metabolic incorporation of d‐amino acids, and the MFO part exhibits peroxidase activity, enabling self‐reporting of bacteria before treatment. The spatial separation of targeting and reporting functions avoids the deterioration of catalytic activity after surface modification. Also important is that MFO facilitates magnetic separation and magnetic heating, leading to easy enrichment and magnetic thermal therapy of labeled bacteria. This method demonstrates that metabolic labeling with d‐amino acids is a promising strategy to specifically target and kill Gram‐positive bacteria.
For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positive Staphylococcus aureus we obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogen Pseudomonas aeruginosa, PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.
We demonstrate herein that corannulene, a bowl‐shaped polycyclic aromatic hydrocarbon, can assemble into larger supramolecular structures in water through a change in the solution temperature. This property is invoked through a simple five‐fold symmetric substitution of the corannulene nucleus with triethylene glycol units. Interestingly, an increase in the solution temperature, which triggers the assembly process, also enhances the fluorescence emission properties of the assembled materials. Although the emission remains very weak in solution, bright green luminescence can be observed in the fibrilar form. This unexpected and interesting behavior indicates that the corannulene nucleus presents a new motif for the design of aggregation‐induced emission (AIE) based luminogens. To the best of our knowledge, this is the first report of a thermoresponsive nonplanar polycyclic hydrocarbon derivative that can respond to a thermal trigger and assemble into larger emissive structures.
Photothermal and photodynamic therapies are established as alternative approaches to combating bacterial infections; however, the heat and reactive oxygen species generated by the photoagents act on both normal and bacterial cells. A targeting strategy is thus required to minimize side effects and enhance the antibacterial efficiency. Glycoconjugates specifically interacting with bacterial lectins have emerged as a new class of materials for targeting bacteria. In this paper, galactosylated plasmonic copper sulfide nanocrystals (Cu 2−x S NCs) are used to target Pseudomonas aeruginosa via galactose-LecA interactions and kill the bacteria by simultaneous photothermal and photodynamic therapy. Galactosylated Cu 2−x S NCs are obtained by functionalizing the nanocrystals with tri-thiogalactoside glycoclusters. The excellent specificity of galactosylated nanoparticles toward LecA with a LecA-deficient P. aeruginosa strain as the control is first demonstrated. Afterward, a laser in the near-infrared II window is used to kill the bacteria, and the critical role of targeted binding in efficient killing of bacteria is highlighted. This approach can be readily generalized to the targeting of other pathogens which have highly specific carbohydrate-binding lectins.
Glycan recognition plays key roles in cell-cell and host-pathogen interactions, stimulating widespread interest in developing multivalent glycoconjugates with superior binding affinity for biological and medical uses. Here, we explore the use of Raman-encoded silver coated gold nanorods (GNRs) as scaffolds to form multivalent glycoconjugates. The plasmonic scaffolds afford high-loading of glycan density and their optical properties offer the possibilities of monitoring and quantitative analysis of glycan recognition. Using E. coli strains with tailored on/off of the FimH receptors, we have demonstrated that Raman-encoded GNRs not only allow for real-time imaging and spectroscopic detection of specific binding of the glycan-GNR conjugates with bacteria of interest, but also cause rapid eradication of the bacteria due to the efficient photothermal conversion of GNRs in the near-infrared spectral window. We envision that optically active plasmonic glycoconjugates hold great potential for screening multivalent glycan ligands for therapeutic and diagnostic applications.
Eight new derivatives of corannulene have been synthesized, characterized, and examined for their water solubility and thermally triggered assembly behavior. To achieve this, the hydrophobic corannulene core was attached to the hydrophilic polyethylene glycol arm(s). Here, the substitution pattern as well as the arm length was varied systematically. Furthermore, the hydrophobic/hydrophilic ratio was adjusted by incorporating a phenyl ring at the junction point of the two moieties. A properties study revealed that a proper balance among the number, length, and chemical nature of the arm was required to ensure water solubility and thermoresponsive character. Remarkably, the lower critical solution temperature could be modulated within the range of 30–50 °C simply through adjusting the molecular structure of the assembling building block. This work, therefore, demonstrates synthetic feasibility of a wide range of amphiphilic corannulene derivatives and opportunity for modulation of their thermoresponsive behavior.
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