Adding Flying Wings: Butterfly-Shaped NIR-II AIEgens with Multiple Molecular Rotors for Photothermal Combating of Bacterial Biofilms

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(47), С. 25705 - 25715

Опубликована: Ноя. 16, 2023

The ever-increasing threats of multidrug-resistant bacteria and their biofilm-associated infections have bred a desperate demand for alternative remedies to combat them. Near-infrared (NIR)-absorbing photothermal agent (PTAs)-mediated therapy (PTT) is particularly attractive biofilm ablation thanks its superiorities noninvasive intervention, satisfactory antibacterial efficiency, less likelihood develop resistance. Herein, three butterfly-shaped aggregation-induced emission luminogens (AIEgens) with balanced nonradiative decay (for conducting PTT) radiative supplying fluorescence in the NIR-II optical window) are rationally designed imaging-assisted obliteration bacterial biofilms. After being encapsulated into cationic liposomes, AIEgens-fabricated nanoparticles can eradicate wide spectrum biofilms formed by Gram-positive (methicillin-resistant Staphylococcus aureus Enterococcus faecalis) Gram-negative (Escherichia coli Pseudomonas aeruginosa) upon an 808 nm laser irradiation. In vivo experiments firmly demonstrate that AIE liposomes excellent biocompatibility perform well both P. aeruginosa biofilm-induced keratitis mouse model MSRA skin infection model.

Язык: Английский

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Potent antibiotic design via guided search from antibacterial activity evaluations

Bioinformatics, Год журнала: 2023, Номер 39(2)

Опубликована: Янв. 27, 2023

Abstract Motivation The emergence of drug-resistant bacteria makes the discovery new antibiotics an urgent issue, but finding molecules with desired antibacterial activity is extremely difficult task. To address this challenge, we established a framework, MDAGS (Molecular Design via Attribute-Guided Search), to optimize and generate potent antibiotic molecules. Results By designing latent space guiding optimization functional compounds based on space, model can novel desirable without need for extensive expensive time-consuming evaluations. Compared existing antibiotics, candidate generated by always possessed significantly better ensured high similarity. Furthermore, although explicit constraints similarity known these all exhibited highest structural expected function in DrugBank database query. Overall, our approach provides viable solution problem bacterial drug resistance. Availability implementation Code datasets be downloaded from GitHub (https://github.com/LiangYu-Xidian/MDAGS). Supplementary information data are available at Bioinformatics online.

Язык: Английский

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High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery

Metabolites, Год журнала: 2023, Номер 13(5), С. 625 - 625

Опубликована: Май 2, 2023

Due to the continued emergence of resistance and a lack new promising antibiotics, bacterial infection has become major public threat. High-throughput screening (HTS) allows rapid large collection molecules for bioactivity testing holds promise in antibacterial drug discovery. More than 50% antibiotics that are currently available on market derived from natural products. However, with easily discoverable being found, finding sources seen limited success. Finding activity also proven be challenging. In addition exploring products synthetic biology, omics technology helped study biosynthetic machinery existing enabling construction unnatural synthesizers bioactive identification molecular targets agents. On other hand, newer smarter strategies have been continuously pursued screen molecule libraries druggable targets. Biomimetic conditions explored mimic real model better ligand–target interaction enable designing more effective drugs. This narrative review describes various traditional contemporaneous approaches high-throughput It further discusses critical factors HTS assay design, makes general recommendation, possible alternatives

Язык: Английский

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Tuning oxidant and antioxidant activities of ceria by anchoring copper single-site for antibacterial application

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 3, 2024

Abstract The reaction system of hydrogen peroxide (H 2 O ) catalyzed by nanozyme has a broad prospect in antibacterial treatment. However, the complex catalytic activities nanozymes lead to multiple pathways reacting parallel, causing uncertain results. New approach effectively regulate is urgent need. Herein, Cu single site modified on nanoceria with various activities, such as peroxidase-like activity (POD) and hydroxyl radical antioxidant capacity (HORAC). Benefiting from interaction between coordinated CeO substrate, POD enhanced while HORAC inhibited, which further confirmed density functional theory (DFT) calculations. Cu-CeO + H shows good properties both vitro vivo. In this work, strategy based metal carrier provides general clue for optimizing nanozymes.

Язык: Английский

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Antimicrobial resistance crisis: could artificial intelligence be the solution?

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Янв. 23, 2024

Abstract Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced priority list of most threatening pathogens against which novel antibiotics need to be developed. The discovery introduction are time-consuming expensive. According WHO’s report antibacterial agents in clinical development, only 18 have been approved since 2014. Therefore, critically needed. Artificial intelligence (AI) rapidly applied drug development its recent technical breakthrough dramatically improved efficiency antibiotics. Here, we first summarized recently marketed antibiotics, antibiotic candidates development. In addition, systematically reviewed involvement AI utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well mechanism prediction, stewardship.

Язык: Английский

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