Efficient Killing of Multidrug‐Resistant Internalized Bacteria by AIEgens In Vivo

Abstract

Bacteria infected cells acting as “Trojan horses” not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden internalized bacteria, especially multidrug‐resistant (MDR) bacteria. Herein, aggregation‐induced emission luminogens (AIEgens) such as N,N‐diphenyl‐4‐(7‐(pyridin‐4‐yl) benzo [c] [1,2,5] thiadiazol‐4‐yl) aniline functionalized with 1‐bromoethane (TBP‐1) and (3‐bromopropyl) trimethylammonium bromide (TBP‐2) (TBPs) show potent broad‐spectrum bactericidal activity against both extracellular and internalized Gram‐positive pathogens. TBPs trigger reactive oxygen species (ROS)‐mediated membrane damage to kill bacteria, regardless of light irradiation. TBPs effectively kill bacteria without the development of resistance. Additionally, such AIEgens activate mitochondria dependent autophagy to eliminate internalized bacteria in host cells. Compared to the routinely used vancomycin in clinic, TBPs demonstrate comparable efficacy against methicillin‐resistant Staphylococcus aureus (MRSA) in vivo. The studies suggest that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.

Bridging D–A type photosensitizers with the azo group to boost intersystem crossing for efficient photodynamic therapy

“…3A, in the absence of white light, there was a moderate concentrationdependent inhibition on bacterial viability, which was attributed to the membrane-damaging effect of cationic species. 45 Upon white light irradiation, the bacterial viability significantly decreased due to the additional destructive effect by the largely generated ROS. In particular, when the concentration of Azo-TPA-Th(+) reached 10 μM, the bacterial killing efficiency was as high as 99.999999%, indicating its outstanding PDT effect.…”

AIEgens for Bacterial Imaging and Ablation

“…[47] Recently, Tang and co-workers studied the antibacterial efficiency of AIEgens and identified the molecular mechanism for enhancing their host cell antibacterial activity (Figure 20). [89] In this contribution, TBPs (TBP-1 and TBP-2) that affected Grampositive bacteria were selected, and the results showed that TBPs had targeted recognition of phosphatidylglycerol (PG) and cardi-olipin (CL). A test of drug resistance suggested that TBPs had a clear target and did not readily generate drug resistance.…”

One-step light-up metabolic probes for in situ discrimination and killing of intracellular bacteria

“…[16][17][18] Cationic AIE-based photosensitizers (PSs) have been previously developed and utilized to detect and kill intracellular bacteria based on electrostatic interactions. [19][20][21][22] Although this kind of AIE PS holds the advantages of simple design and fast detection, its selectivity may be highly limited due to the non-specific interactions with the surrounding environments. Another concern is the appropriate tuning of cationic charges and hydrophobicity.…”