De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation.

IF 11.3 1区 医学 Q1 Medicine Biomaterials Research Pub Date : 2023-03-13 DOI:10.1186/s40824-023-00359-w
Xueyan Huang, Fei Chen, Yeshuo Ma, Fan Zheng, Yanpeng Fang, Bin Feng, Shuai Huang, Hongliang Zeng, Wenbin Zeng
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引用次数: 1

Abstract

Background: Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. Additionally, in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization.

Methods: We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo.

Results: ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish.

Conclusions: ASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research.

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一种新型AIE荧光探针的从头设计,通过pH操作定制自噬可视化。
背景:巨噬是一种重要的细胞自我保护机制,巨噬缺陷被认为与多种疾病有关。在此过程中,细胞质成分通过自噬体转运到酸性溶酶体进行代谢和再循环,这代表了溶酶体靶向荧光探针的应用利基。此外,由于自噬途径的复杂性,对适合监测自噬的探针提出了更严格的要求。同时,聚集诱导发射(AIE)荧光探针在生物医学领域得到了广泛的应用,为自噬可视化带来了令人着迷的可能性。方法:我们报道了一种新的ph敏感AIE探针asp - ap的通用从头设计,该探针专为溶酶体靶向解释自噬而量身定制。首先进行了理论计算,然后进行了光学性质研究。然后,通过饥饿或药物治疗证实ASMP-AP在自噬可视化中的表现。此外,在离体肝组织和斑马鱼体内,ASMP-AP具有监测自噬的能力。结果:ASMP-AP具有较大的心肌位移、细胞渗透性和良好的生物相容性。更重要的是,ASMP-AP对pH有很好的线性响应,这是因为它的聚集状态可以被酸度控制。它成功地应用于活细胞自噬成像,并被证明具有监测线粒体自噬的能力。此外,通过药物性肝损伤模型激活自噬的体外可视化验证了这种新的分子工具。有趣的是,它提供了一个有意义的药理学见解,黑色素抑制剂1-苯基-2-硫脲(PTU)诱导的自噬在野生型斑马鱼中明显存在。结论:ASMP-AP为研究溶酶体和自噬提供了一种简单而有效的工具。这是首次使用具有AIE特征的小分子探针,精确的溶酶体靶向和同时的pH敏感性来可视化斑马鱼的自噬。最终,这种新型荧光系统具有巨大的体内翻译潜力,可以为自噬研究提供燃料。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomaterials Research
Biomaterials Research Medicine-Medicine (miscellaneous)
CiteScore
10.20
自引率
3.50%
发文量
63
审稿时长
30 days
期刊介绍: Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.
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