文献:线粒体、溶酶体和内质网:哪个是光疗的最佳靶点?
链接:https://www.sciencedirect.com/science/article/abs/pii/S0168365922006320
作者:李艳红 ,贾浩然 ,王洪 银,华先武 ,鲍彦文 ,吴福 根
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摘要
光动力疗法(PDT) 是一种强大的癌症治疗方式,其亚细胞作用位点的精确时空控制对其有效性至关重要。然而,准确比较不同细胞器靶向 PDT 方法的疗效具有挑战性,因为很难找到一个单一的系统能够实现对不同细胞器的单独靶向性、可分离的时间窗和相似的结合量。在此,我们将二氢卟酚 e6 (Ce6) 与 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N- [氨基(聚乙二醇)-5000](铵盐)(DSPE-PEG 5000 -NH 2)偶联得到 DSPE-PEG-Ce6,其在细胞内化后可以从线粒体迁移到溶酶体,最终到内质网 (ER)。得益于DSPE-PEG-Ce6亚细胞分布的动态性以及其与细胞器结合量的可调性,我们准确地确定了该分子的光动力治疗(PDT)疗效顺序,即线粒体 > 内质网 > 溶酶体。本研究提出了一个理想的模型系统,可用于准确评估特定细胞器靶向的光动力治疗(PDT)疗效,并有望促进未来有效光动力治疗策略的发展。
Abstract
Photodynamic therapy (PDT) is a robust cancer treatment modality, and the precise spatiotemporal control of its subcellular action site is crucial for its effectiveness. However, accurate comparison of the efficacy of different organelle-targeted PDT approaches is challenging since it is difficult to find a single system that can achieve separate targeting of different organelles with separable time windows and similar binding amounts. Herein, we conjugated chlorin e6 (Ce6) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (ammonium salt) (DSPE-PEG5000-NH2) to afford DSPE-PEG-Ce6, which could migrate from mitochondrion to lysosome and ultimately to endoplasmic reticulum (ER) after cellular internalization. Benefiting from the dynamic subcellular distribution of DSPE-PEG-Ce6 with tunable organelle-binding amounts, we accurately determined the PDT efficacy order of the molecule, i.e., mitochondrion > ER > lysosome. This work proposes an ideal model system for accurately evaluating the specific organelle-targeted PDT efficacy and may promote the future development of effective PDT strategies.
西安齐岳生物提供相关产品:
SP94-PEG-DSPE
T7(HAIYPRH)-PEG-DSPE
Octreotide-PEG-DSPE
YIGSR-PEG-DSPE
APRPG-PEG-DSPE
NGR-PEG-DSPE
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