School of Physical Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi 110016, India.
ACS Appl Mater Interfaces. 2020 Aug 12;12(32):35967-35976. doi: 10.1021/acsami.0c11161. Epub 2020 Jul 28.
Antimicrobial resistance has become a major threat to public health due to the rampant and empirical use of antibiotics. Rapid diagnosis of bacteria with the desired sensitivity and selectivity still, however, remains an open challenge. We report a special class of water-soluble metal-based aggregation-induced emission luminogens (AIEgens), namely, cyclometalated iridium(III) polypyridine complexes of the type [Ir(PQ)(N^N)]Cl (-), where PQ = 2-phenylquinoline and N^N = 2,2'-bipyridine derivatives, that demonstrate dual capability for detection and elimination of drug-resistant bacteria in aqueous solutions. These AIEgens exhibit selective and rapid sensing of endotoxins, such as lipopolysaccharides (LPS) and lipoteichoic acid (LTA) released by the bacteria, with a detection limit in the lower nanomolar range. Targeting these naturally amplified biomarkers (approximately 1 million copies per cell) by iridium(III) complexes induces strong AIE in the presence of different Gram-negative and Gram-positive bacteria including carbapenem-resistant (CRAB) and methicillin-resistant (MRSA) at concentrations as low as 1.2 CFU/mL within 5 min in spiked water samples. Detection of bacteria by the complexes is also visible to the naked eye at higher (10 CFU/mL) cell concentrations. More notably, complexes and show potent antibacterial activity against drug-resistant bacteria with low minimum inhibitory concentrations (MICs) ≤ 5 μg/mL (1-4 μM) via ROS generation and cell membrane disintegrity. To the best of our knowledge, this work is the "first-in-class" example of a metal-based theranostic system that integrates selective, sensitive, rapid, naked-eye, wash-free, and real-time detection of bacteria using broad-spectrum antibiotics into a single platform. This dual capability of AIEgens makes them ideal scaffolds for monitoring bacterial contamination in aqueous samples and pharmaceutical applications.
由于抗生素的广泛和经验性使用，抗微生物耐药性已成为公共卫生的主要威胁。然而，仍然迫切需要快速诊断具有所需敏感性和选择性的细菌。我们报告了一类特殊的水溶性金属基聚集诱导发射发光体（AIEgen），即金属铱（III）多吡啶配合物[Ir(PQ)(N^N)]Cl(-)，其中 PQ = 2-苯基喹啉，N^N = 2,2'-联吡啶衍生物，它们在水溶液中具有检测和消除耐药细菌的双重能力。这些 AIEgen 对细菌释放的内毒素（如脂多糖（LPS）和脂磷壁酸（LTA））表现出选择性和快速的传感，检测限在纳摩尔范围内。通过铱（III）配合物靶向这些天然扩增的生物标志物（每个细胞约 100 万个拷贝），在存在不同革兰氏阴性和革兰氏阳性细菌（包括碳青霉烯耐药（CRAB）和耐甲氧西林金黄色葡萄球菌（MRSA））的情况下，在 5 分钟内可在掺杂水样中以低至 1.2 CFU/mL 的浓度诱导强烈的 AIE。在更高的（10 CFU/mL）细胞浓度下，复合物也可以肉眼检测到细菌。更值得注意的是，配合物 和 对耐药细菌表现出强大的抗菌活性，最低抑菌浓度（MIC）低至 5 μg/mL（1-4 μM），通过 ROS 生成和细胞膜完整性破坏。据我们所知，这是第一个将广谱抗生素选择性、灵敏、快速、肉眼、免洗和实时检测细菌的基于金属的治疗系统整合到单个平台中的范例。AIEgen 的这种双重能力使它们成为监测水溶液中细菌污染和药物应用的理想支架。
