Disrupting tumor onset and growth via selective cell tagging (SeCT) therapy.

Disrupting tumor onset and growth via selective cell tagging (SeCT) therapy.
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DOI:
10.1126/sciadv.abg4038
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发表时间:
2021-04
期刊:
影响因子:
13.6
通讯作者:
Tanaka K
Tanaka K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Vong K;Tahara T;Urano S;Nasibullin I;Tsubokura K;Nakao Y;Kurbangalieva A;Onoe H;Watanabe Y;Tanaka K

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小鼠中的HeLa癌细胞可以用治疗性部分在体内标记,从而破坏肿瘤的发作或生长。这项研究提出了选择性细胞标记(SeCT)治疗的早期框架,这是一个概念,优先标记特定的细胞在体内与化学部分,可以引起治疗反应。使用糖基化人工金属酶(GArM)为基础的蛋白质标记,这项研究报告了两个独立的功能策略。在一种方法中,可以通过用整联蛋白阻断性环状-Arg-Gly-Asp(cRGD)部分标记活小鼠中的癌细胞来抑制早期肿瘤发作,从而破坏细胞粘附到细胞外基质上。在另一种方法中,可以通过用细胞毒性多柔比星部分标记来减少小鼠中的肿瘤生长。随后的细胞死亡发生在内化和药物释放之后。总体而言,实验表明,与对照相比,接受SeCT标记试剂混合物的小鼠群体表现出肿瘤发作和生长的显著延迟/减少。这项工作突出了其适应性,代表了SeCT疗法及其潜在治疗应用的进一步发展的基础性步骤。
HeLa cancer cells in mice can be tagged in vivo with therapeutic moieties, thereby disrupting either tumor onset or growth. This study presents the early framework of selective cell tagging (SeCT) therapy, which is the concept of preferentially labeling specific cells in vivo with chemical moieties that can elicit a therapeutic response. Using glycosylated artificial metalloenzyme (GArM)–based protein labeling, this study reports two separate functional strategies. In one approach, early tumor onset can be suppressed by tagging cancer cells in living mice with an integrin-blocking cyclic–Arg-Gly-Asp (cRGD) moiety, thereby disrupting cell adhesion onto the extracellular matrix. In another approach, tumor growth in mice can be reduced by tagging with a cytotoxic doxorubicin moiety. Subsequent cell death occurs following internalization and drug release. Overall, experiments have shown that mouse populations receiving the mixture of SeCT labeling reagents exhibited a significant delay/reduction in tumor onset and growth compared with controls. Highlighting its adaptability, this work represents a foundational step for further development of SeCT therapy and its potential therapeutic applications.
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