A Bifunctional Aggregation‐Induced Emission Luminogen for Monitoring and Killing of Multidrug‐Resistant Bacteria

Abstract

Multidrug‐resistant (MDR) bacteria pose serious threats to public health as there is currently a lack of effective and biocompatible drugs to kill MDR bacteria. Here, a bifunctional aggregation‐induced emission luminogen (AIEgen), triphenylethylene‐naphthalimide triazole (TriPE‐NT), is reported, which is capable of both staining and killing Gram‐positive (G+) and Gram‐negative (G−) bacteria. The intrinsic fluorescence generating ability of the TriPE unit enables TriPE‐NT to monitor the drug–bacteria interactions, meanwhile, the NT unit renders TriPE‐NT the antibacterial activity. Furthermore, TriPE‐NT can generate reactive oxygen species (ROS) under light irradiation and drastically enhance its antibacterial efficacy by photodynamic therapy against wild bacteria and clinical isolated MDR bacteria with a very low toxicity to mammalian cells. Moreover, the efficiency of TriPE‐NT staining on bacteria closely correlates with its antibacterial efficacy. As an example of application, TriPE‐NT is utilized in curing Escherichia coli‐ (E. coli), MDR E. coli‐, Staphylococcus epidermidis‐ (S. epidermidis), and MDR S. epidermidis‐ infected wounds on rats with high efficacy and high safety. Thus, TriPE‐NT can be used not only as a powerful antibiotic agent for treating MDR bacteria‐infected diseases but also as a potential fluorescent agent for monitoring the bacterial infections and further exploring the related antibacterial mechanism.

Rejuvenated Photodynamic Therapy for Bacterial Infections

“…Furthermore, these PSs retain the efficient capacity of ROS generation in the aggregation states . For example, Tang's group developed triphenylethylene‐naphthalimide triazole (TriPE‐NT), which exhibited excellent fluorescent characteristic ( Figure a) and ROS generating capability (Figure b) in the aggregation states . The FL and scanning electron microscopy (SEM) images in Figure c indicate that TriPE‐NT interacted with the bacterial cell membrane of E. coli and then destructed the bacteria in the presence of white light.…”

“…c) FL and SEM images of E. coli performed with TriPE‐NT to monitor and treat the bacterial infections. Reproduced with permission . Copyright 2018, Wiley‐VCH.…”

Selective Photoinactivation of Methicillin‐Resistant Staphylococcus aureus by Highly Positively Charged RuII Complexes

“…ROS, mainly singlet oxygen ( 1 O 2 ), are highly reactive and can damage DNA, proteins, and lipids effectively . The multi‐target feature of ROS not only renders aPDT highly potent in killing even multidrug resistant bacteria, but also makes bacteria difficult to develop any resistance against these multiple attacks …”

“…[8] The multi-target feature of ROS not only renders aPDT highlyp otent in killing even multidrug resistantb acteria, but also makes bacteria difficult to develop any resistance against these multiplea ttacks. [9][10][11] However,t he same modes of action of PDT and aPDT raise a great challenge in selectively inactivating bacterialc ells but leavingm ammalian cells unaffected.U nlike mammalian cells, in whicha cidic phospholipidsa re mainly located in the inner leafleto fp lasma membranes, acidic phospholipids andn egatively chargedc omponents, such as teichuronic acid (for Gram positive bacteria, for example, S. aureus)a nd lipopolysaccharide (for Gram negative bacteria, for example, E. coli)a re mainly locatedi nt he outer edges of cell walls or outer membranes, making the bacterial surface highly negatively charged. [12,13] This disparity has been leveraged to develop cationic aPDT agents, such as triarylmethanes [14,15] and borondipyrromethene (BODIPY)d yes bearing two positive charges, [16] peryleneb earing four positive charges, [17] porphyrins, [18][19][20][21][22][23] phthalocyanines [24] and bacteriochlorin [25,26] bearing three, four, or eight positive charges, with the aim to achieve higher binding affinity toward bacteria.T hough these photosensitizers showed remarkable inactivation capability against bacterial cells, in several cases, phototoxicity towardm ammalianc ells was observed, [14,23] suggestingl imited selectivity of the aPDT agents.…”

Silver‐Infused Porphyrinic Metal–Organic Framework: Surface‐Adaptive, On‐Demand Nanoplatform for Synergistic Bacteria Killing and Wound Disinfection

“…This distinctive approach is based on the use of photosensitizers (PSs) under appropriate light irradiation to generate reactive oxygen species (ROS). The generated ROS reacts with a large number of biological substrates, like lipids, proteins, DNA, and RNA, to alter their structures chemically, which thus affects the activity of the bacteria and leads to bacterial death ultimately . In particular, owing to the excellent photophysical properties, porphyrin family is popularly employed as one class of important photosensitizers .…”