Multifunctional Glyco-Nanosheets to Eradicate Drug-Resistant Bacteria on Wounds.

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.

Synthetic biohybrid peptidoglycan oligomers enable pan-bacteria-specific labeling and imaging: in vitro and in vivo.

Peptidoglycan is the core component of the bacterial cell wall, which makes it an attractive target for the development of bacterial targeting agents. Intercepting its enzymatic assembly with synthetic substrates allows for labeling and engineering of live bacterial cells. Over the past two decades, small-molecule-based labeling agents, such as antibiotics, d-amino acids or monosaccharides have been developed for probing biological processes in bacteria. Herein, peptidoglycan oligomers, substrates for transglycosylation, are prepared for the first time using a top-down approach, which starts from chitosan as a cheap feedstock. A high efficiency of labeling has been observed in all bacterial strains tested using micromolar substrates. In contrast, uptake into mammalian cells was barely observable. Additional mechanistic studies support a hypothesis of bacteria-specific metabolic labeling rather than non-specific binding to the bacterial surface. Eventually, its practicality in bacterial targeting capability is demonstrated in resistant strain detection and in vivo infection models.

Stimuli-responsive multifunctional glyconanoparticle platforms for targeted drug delivery and cancer cell imaging.

Targeted bioimaging or chemotherapeutic drug delivery to achieve the desired therapeutic effects while minimizing side effects has attracted considerable research attention and remains a clinical challenge. Presented herein is a multi-component delivery system based on carbohydrate-functionalized gold nanoparticles conjugated with a fluorophore or prodrug. The system leverages active targeting based on carbohydrate-lectin interactions and release of the payload by biological thiols. Cell-type specific delivery of the activatable fluorophore was examined by confocal imaging on HepG2 cells, and displays distinct selectivity towards HepG2 cells over HeLa and NIH3T3 cells. The system was further developed into a drug delivery vehicle with camptothecin (CPT) as a model drug. It was demonstrated that the complex exhibits similar cytotoxicity to that of free CPT towards HepG2 cells, and is significantly less cytotoxic to normal HDF and NIH3T3 cells, indicating excellent specificity. The delivery vehicle itself exhibits excellent biocompatibility and offers an attractive strategy for cell-type specific delivery depending on the carbohydrates conjugated in the system.