Metabolic labeling mediated targeting and thermal killing of Gram-positive bacteria by self-reporting Janus magnetic nanoparticles

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/MnFe2 O4 (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.Ministry of Education (MOE)This work was funded and supported by Ministry of Education-Singapore (MOE2013-T3-1-002, MOE2018-T3-1-003, MOE2018-T2-2-128, and RG45/18)

Glycosylated copper sulfide nanocrystals for targeted photokilling of bacteria in the near‐infrared II window

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 (Cu2−xS NCs) are used to target Pseudomonas aeruginosa via galactose–LecA interactions and kill the bacteria by simultaneous photothermal and photodynamic therapy. Galactosylated Cu2−xS 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.MOE (Min. of Education, S’pore)MOH (Min. of Health, S’pore)Accepted versio

A general approach to non-fullerene electron acceptors based on the corannulene motif

Here, we show that oxidation of exo-cyclic sulfur atoms enhances the molecular reduction potential of non-planar polycyclic aromatic hydrocarbons and allows for a systematic bridging of the electron affinity gap between corannulene, a fragment of fullerene C₆₀, and the prevalent fullerene-based electron acceptor phenyl-C₆₁-butyric acid methyl ester (PCBM).Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversitySupport from the MoE under the AcRF Tier 1 (M4011792) (M4012047); A*STAR AME IRG A1883c0006; and NTU (M4081566) is gratefully acknowledged. J. H. thanks Creative Materials Discovery Program through the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (2018M3D1A1058536)

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.ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)Accepted versio

Raman-encoded, multivalent glycan-nanoconjugates for traceable specific binding and killing of bacteria

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.MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Accepted versio