School of Chemistry, Dalian University of Technology, Dalian, 116024, China.
School of Chemistry, Dalian University of Technology, Dalian, 116024, China.
Anal Chim Acta. 2024 Jan 25;1287:342063. doi: 10.1016/j.aca.2023.342063. Epub 2023 Nov 24.
Single oxygen (O), the molecular oxygen at its excited state, plays a crucial role in the photodynamic therapy (PDT) of some diseases owing to its strong oxidizing property to destroy malignant cells. Although the fluorescent probe technique has proven its powerful application abilities for detection of O in biological systems, most of the reported fluorescent probes suffered from the interference of background autofluorescence of biological samples. It is clear that the real-time and in situ, background-free fluorescent detection of O generated in live cells, especially in some organelles, is of great significance for understanding the action mechanism of PDT drugs.
By introducing a lysosome-anchoring motif, a morpholine moiety, into a O-specifically-reactive terpyridine polyacid ligand, [4'-(9-anthryl)-2,2':6',2″-terpyridine-6,6″-diyl] bis(methylenenitrilo) tetrakis (acetic acid) (ATTA), and chelating with lanthanide ions (Eu or Tb), two lanthanide complex-based "turn-on" luminescent probes that can be used for the background-free time-gated luminescent (TGL) detection of lysosomal O, Lyso-ATTA-Eu and Lyso-ATTA-Tb, have been developed. The probes exhibit fast luminescence responses (within 2.5 min) towards O with high selectivity and sensitivity (<0.75 μM) in a wide pH range (4-11). And the excellent lysosome-localization performance of the probes allowed them to be used for the monitoring of endogenous O in lysosomes, which enabled the variability of lysosomal-O concentrations induced by different photosensitizers to be successfully discriminated. Furthermore, by doping Lyso-ATTA-Eu into the polyethylene glycol (PEG) hydrogel, the smart luminescent sensor film, PEG-Lyso-ATTA-Eu, was prepared, and successfully used for the detection of the on-site O production during the PDT process of psoriatic disease in model mice.
Two lysosome-targetable background-free TGL probes for O were firstly reported. The developed smart luminescent sensor film could be a powerful tool for the clinical monitoring of PDT on skin diseases without using sophisticated and expensive instruments.
单重态氧（O）是分子氧的激发态，由于其强氧化性，能够破坏恶性细胞，因此在某些疾病的光动力疗法（PDT）中发挥着关键作用。尽管荧光探针技术已被证明在生物系统中检测 O 方面具有强大的应用能力，但大多数报道的荧光探针都受到生物样品背景荧光的干扰。显然，实时、原位、无背景的活细胞中产生的 O 的荧光检测，特别是在某些细胞器中，对于理解 PDT 药物的作用机制具有重要意义。
通过将溶酶体锚定基序（一个吗啉基）引入到一个对 O 具有特异性反应的三吡啶多酸配体[4'-(9-蒽基)-2,2':6',2″-三吡啶-6,6″-二基]双(亚甲基亚氨基)四乙酸（ATTA）中，并与镧系离子（Eu 或 Tb）螯合，开发了两种基于镧系元素配合物的“开启”发光探针，可用于无背景时间门控发光（TGL）检测溶酶体中的 O，即 Lyso-ATTA-Eu 和 Lyso-ATTA-Tb。探针在宽 pH 范围（4-11）内对 O 具有快速的发光响应（<0.75 μM），且具有高选择性和灵敏度。此外，探针具有良好的溶酶体定位性能，可用于监测溶酶体中的内源性 O，从而成功区分了不同光敏剂诱导的溶酶体-O 浓度的变化。此外，通过将 Lyso-ATTA-Eu 掺杂到聚乙二醇（PEG）水凝胶中，制备了智能发光传感器膜 PEG-Lyso-ATTA-Eu，并成功用于模型小鼠银屑病 PDT 过程中现场 O 生成的检测。
首次报道了两种溶酶体靶向的无背景 TGL O 探针。所开发的智能发光传感器膜可作为一种强大的工具，用于皮肤疾病 PDT 的临床监测，而无需使用复杂且昂贵的仪器。
