Intracellular bacterial (ICB) infection is one of the most life‐threatening cases of drug resistance, and photodynamic therapy (PDT) is challenged by limited light penetration into tissues and unspecific toxicity to host cells. Herein, theranostic nanoparticles (NPs) are developed to facilitate on‐demand activation of photosensitizers inside ICBs and persistent PDT of deep‐tissue ICB infections. Mechanoluminescent SrAl2O4:Eu2+ and persistence luminescent CaS:Eu2+ are sequentially deposited on mesoporous silica to prepare mSC, followed by encapsulation by bacterial membranes with loaded nitroreductase (NTR)‐activatable methylene blue (nMB) to obtain mSC‐nMB@BM NPs. The fluorescence quenching of nMB with mSC offers few cytotoxicities even under ultrasonication, and bacterial membrane coatings mediate the specific NP internalization into ICB‐infected macrophages. Bacterial pore‐forming toxins trigger nMB release from NPs, and intrabacterial NTR rejuvenates methylene blue probes from nMB for real‐time imaging of ICB infections. Ultrasonication of NPs continuously excites the rejuvenated methylene blue to generate reactive oxidative species and reduce viable ICBs by 3.54 log magnitude folds. NP treatment on ICB‐infected mice exhibits full survival and restores viscera functions without any pathological abnormality. Therefore, this concise NP design demonstrates capabilities of bacterial membrane‐mediated specific internalization, bacterial toxin‐triggered release and intrabacterial NTR‐rejuvenation of fluorescent probes, and persistent internal light‐illumination for ICB theranostics.

中文翻译：

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用于细胞内感染治疗诊断的细菌内硝基还原酶激活成像和持续照明光动力疗法


细胞内细菌（ICB）感染是最危及生命的耐药性病例之一，光动力疗法（PDT）面临组织光穿透有限和对宿主细胞非特异性毒性的挑战。在此，开发了治疗诊断纳米颗粒（NP），以促进 ICB 内光敏剂的按需激活和深部组织 ICB 感染的持续 PDT。将机械发光SrAl2O4:Eu2+和持久发光CaS:Eu2+依次沉积在介孔二氧化硅上制备mSC，然后用负载硝基还原酶（NTR）激活亚甲蓝（nMB）的细菌膜封装以获得mSC-nMB@BM NPs。即使在超声处理下，nMB 的荧光猝灭也几乎没有细胞毒性，并且细菌膜涂层介导特定的 NP 内化到 ICB 感染的巨噬细胞中。细菌成孔毒素触发 NP 释放 nMB，细菌内 NTR 使 nMB 中的亚甲蓝探针恢复活力，用于 ICB 感染的实时成像。 NP 的超声波处理持续激发再生的亚甲基蓝，产生活性氧化物质，并将活性 ICB 减少 3.54 个对数级。 NP 治疗 ICB 感染的小鼠表现出完全存活并恢复内脏功能，没有任何病理异常。因此，这种简洁的 NP 设计展示了细菌膜介导的特异性内化、细菌毒素触发释放和荧光探针的细菌内 NTR 复兴以及 ICB 治疗诊断的持续内部光照明的能力。