Abstract：
Methicillin-resistant Staphylococcus aureus (MRSA) causes great health hazards to society because most antibiotics are ineffective. Photodynamic treatment (PDT) has been proposed to combat MRSA due to the advantage of imaging-guided no-drug resistance therapy. However, the traditional photosensitizers for PDT are limited by aggregation-caused quenching for imaging and low photodynamic antibacterial efficiency. In this work, we synthesize a new aggregation-induced emission (AIE) photosensitizer (APNO), which can ultrafast distinguish between Gram-positive and Gram-negative bacteria within 3 s by AIE-active photosensitizer imaging. Meanwhile, APNO can generate antibacterial reactive oxygen species under light irradiation, which holds potential for antibacterial PDT. Then, APNO is loaded by PHEAA hydrogel to obtain a highly efficient photodynamic hydrogel (APNO@gel). In vitro results show complete inhibition of MRSA by APNO@gel under lower-power light irradiation. Transcriptome analysis is performed to investigate antibacterial mechanism of APNO@gel. Most importantly, APNO@gel also exhibits significant inhibition and killing ability of MRSA in the MRSA wound infection model, which will further promote rapid wound healing. Therefore, the photodynamic hydrogel provides a promising strategy toward MRSA ultrafast imaging and killing.
摘要：
耐甲氧西林金黄色葡萄球菌（MRSA）对社会健康造成极大危害，因为大多数抗生素无效。由于成像引导的无耐药性治疗的优势，已经提出了光动力治疗（PDT）来对抗MRSA。然而,用于PDT的传统光敏剂受限于聚集引起的成像猝灭和低光动力抗菌效率。在这项工作中,我们合成了一种新的聚集诱导发射（AIE）光敏剂（APNO），通过AIE活性光敏剂成像可以在3s内快速区分革兰氏阳性和革兰氏阴性细菌。同时,APNO能在光照下产生抗菌活性氧,具有抗菌PDT的潜力。然后，APNO负载PHEAA水凝胶获得高效的光动力水凝胶(APNO@gel)。体外结果表明，在较低功率的光照下，APNO@凝胶完全抑制了MRSA。进行转录组分析以研究APNO@凝胶的抗菌机制。最重要的是,在MRSA伤口感染模型中,APNO@gel对MRSA也表现出显著的抑制和杀伤能力,这将进一步促进伤口的快速愈合。因此,光动力水凝胶为MRSA超快成像和杀伤提供了有希望的策略。
