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精心设计的碳点作为光触发的 RNA 破坏剂,引发细胞焦亡。

Meticulously Designed Carbon Dots as Photo-Triggered RNA-Destroyer for Evoking Pyroptosis.

机构信息

School of Chemistry and Chemical Engineering, Anhui University, Hefei, Anhui 230601, China.

School of Materials Science and Engineering, Anhui University, Hefei, Anhui 230601, China.

出版信息

Bioconjug Chem. 2023 Aug 16;34(8):1387-1397. doi: 10.1021/acs.bioconjchem.3c00278. Epub 2023 Aug 3.

Abstract

An ideal photosensitizer for photodynamic therapy should not only possess high reactive oxygen species (ROS) generation efficiency but also maximize utilization of the in situ produced ROS species, where the latter is closely related to its intracellular location. However, rational design of such photosensitizer without tedious conjugation procedures remains a grand challenge. Here, we report the one-pot preparation of carbon dots (CDs)-based photosensitizer from levofloxacin and neutral red featuring both high O quantum yield (φ = 38.85%) and superior RNA selectivity. Moreover, the φ value shows a further 40% improvement and reaches 54.33% in response to RNA binding. Owing to these combined attributes, the CDs could exert great damage to the cellular RNA system (termed the RNA-destroyer) under extremely low dosage of light irradiation (15 mW cm, 1 min). It induces pyroptotic cell death and causes rapid release of different cytokines that served as molecular markers in photodynamic immunotherapy. This work represents the meticulously designed CDs with high ROS generation and utilization efficiency via good organization of the photosensitive and targeting modularity. Moreover, it is the first CDs-based pyroptosis inducer to the best of our knowledge.

摘要

用于光动力疗法的理想光敏剂不仅应具有高效的活性氧(ROS)生成效率,还应最大限度地利用原位产生的 ROS 种类,后者与光敏剂的细胞内位置密切相关。然而,在无需繁琐偶联步骤的情况下,合理设计此类光敏剂仍然是一个巨大的挑战。在这里,我们报告了一种从左氧氟沙星和中性红一锅法制备的基于碳点(CDs)的光敏剂,其具有高 O 量子产率(φ = 38.85%)和优异的 RNA 选择性。此外,在与 RNA 结合时,φ 值进一步提高了 40%,达到 54.33%。由于这些综合特性,在极低剂量的光照射(15 mW cm,1 分钟)下,CDs 可以对细胞 RNA 系统(称为 RNA 破坏剂)造成巨大的损伤。它诱导细胞发生细胞焦亡,并导致不同细胞因子的快速释放,这些细胞因子可作为光动力免疫治疗中的分子标志物。这项工作代表了通过良好的光敏和靶向模块组织,具有高效 ROS 生成和利用效率的精心设计的 CDs。此外,据我们所知,这是第一个基于 CDs 的细胞焦亡诱导剂。

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