In vivo metal-catalyzed SeCT therapy by a proapoptotic peptide.

In vivo metal-catalyzed SeCT therapy by a proapoptotic peptide.
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DOI:
10.1039/d1sc01784e
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发表时间:
2021-09-29
期刊:
影响因子:
8.4
通讯作者:
Tanaka K
Tanaka K
中科院分区:
化学1区
文献类型:
--
作者:
Ahmadi P;Muguruma K;Chang TC;Tamura S;Tsubokura K;Egawa Y;Suzuki T;Dohmae N;Nakao Y;Tanaka K

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选择性细胞标记(Selective cell tagging, SeCT)疗法是一种通过催化化学转化将特定的化学成分标记在目标细胞上以达到治疗效果的方法。在此,我们报道了一种基于促凋亡肽(Ac-GGKLFG-X; X =反应性组)靶向细胞表面标记的癌症治疗方法,当它附着在细胞表面时诱导细胞凋亡。通过金催化酰胺化或钌催化烷基化,这些促凋亡肽在体外和体内均显示出良好的治疗效果。特别是与促凋亡肽和载体- ru复合物共处理,单次注射即可显著协同抑制肿瘤生长,延长荷瘤小鼠存活率。这是Ru催化剂在体内应用的第一篇报道,该方法可用于肿瘤的SeCT治疗。单次注射后,带有共价标记的促凋亡肽和载体- ru复合物联合使用可抑制小鼠肿瘤生长。
Selective cell tagging (SeCT) therapy is a strategy for labeling a targeted cell with certain chemical moieties via a catalytic chemical transformation in order to elicit a therapeutic effect. Herein, we report a cancer therapy based on targeted cell surface tagging with proapoptotic peptides (Ac-GGKLFG-X; X = reactive group) that induce apoptosis when attached to the cell surface. Using either Au-catalyzed amidation or Ru-catalyzed alkylation, these proapoptotic peptides showed excellent therapeutic effects both in vitro and in vivo. In particular, co-treatment with proapoptotic peptide and the carrier–Ru complex significantly and synergistically inhibited tumor growth and prolonged survival rate of tumor-bearing mice after only a single injection. This is the first report of Ru catalyst application in vivo, and this approach could be used in SeCT for cancer therapy. The combination of a proapoptotic peptide with covalent tagging and a carrier-Ru-complex inhibited tumor growth in mice after a single injection.
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