Vong Kenward, Tahara Tsuyoshi, Urano Sayaka, Nasibullin Igor, Tsubokura Kazuki, Nakao Yoichi, Kurbangalieva Almira, Onoe Hirotaka, Watanabe Yasuyoshi, Tanaka Katsunori
Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
GlycoTargeting Research Laboratory, RIKEN Baton Zone Program, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Sci Adv. 2021 Apr 23;7(17). doi: 10.1126/sciadv.abg4038. Print 2021 Apr.
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.
本研究提出了选择性细胞标记（SeCT）疗法的早期框架，该疗法的概念是在体内用能够引发治疗反应的化学基团优先标记特定细胞。利用基于糖基化人工金属酶（GArM）的蛋白质标记，本研究报告了两种不同的功能策略。在一种方法中，通过用整合素阻断性环-精氨酸-甘氨酸-天冬氨酸（cRGD）基团标记活体小鼠体内的癌细胞，可抑制肿瘤早期发生，从而破坏细胞与细胞外基质的黏附。在另一种方法中，通过用细胞毒性阿霉素基团进行标记，可减少小鼠体内肿瘤的生长。内化和药物释放后会发生后续的细胞死亡。总体而言，实验表明，与对照组相比，接受SeCT标记试剂混合物的小鼠群体的肿瘤发生和生长出现了显著延迟/减缓。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进一步发展的基础步骤。
