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通过自报告光敏剂原位监测细胞凋亡过程。

In Situ Monitoring Apoptosis Process by a Self-Reporting Photosensitizer.

机构信息

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Institute for Advanced Study, Institute of Molecular Functional Materials, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemical and Biological Engineering , The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon , Hong Kong , China.

Department of Chemistry , City University of Hong Kong , Hong Kong , China.

出版信息

J Am Chem Soc. 2019 Apr 10;141(14):5612-5616. doi: 10.1021/jacs.9b00636. Epub 2019 Apr 2.

Abstract

Although photodynamic therapy (PDT) has thrived as a promising treatment, highly active photosensitizers (PSs) and intense light power can cause treatment overdose. However, extra therapeutic response probes make the monitoring process complicated, ex situ and delayed. Now, this challenge is addressed by a self-reporting cationic PS, named TPE-4EP+, with aggregation-induced emission characteristic. The molecule undergoes mitochondria-to-nucleus translocation during apoptosis induced by PDT, thus enabling the in situ real-time monitoring via fluorescence migration. Moreover, by molecular charge engineering, we prove that the in situ translocation of TPE-4EP+ is mainly attributed to the enhanced interaction with DNA imposed by its multivalent positive charge. The ability of PS to provide PDT with real-time diagnosis help control the treatment dose that can avoid excessive phototoxicity and minimize potential side effect. Future development of new generation of PS is envisioned.

摘要

尽管光动力疗法(PDT)作为一种很有前途的治疗方法而蓬勃发展,但高活性光敏剂(PS)和高强度光功率可能会导致治疗过度。然而,额外的治疗反应探针使监测过程变得复杂、非原位和延迟。现在,一种自报告的阳离子 PS,名为 TPE-4EP+,具有聚集诱导发射特性,解决了这一挑战。该分子在 PDT 诱导的细胞凋亡过程中发生从线粒体到细胞核的转位,从而通过荧光迁移实现了原位实时监测。此外,通过分子电荷工程,我们证明 TPE-4EP+的原位转位主要归因于其多价正电荷与 DNA 之间增强的相互作用。PS 提供 PDT 实时诊断的能力有助于控制治疗剂量,从而避免过度光毒性并最小化潜在的副作用。可以预见新一代 PS 的发展。

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