Kenward Vong 1 , 2 , Tsuyoshi Tahara 3 , 4 , Sayaka Urano 1 , Igor Nasibullin 1 , 5 , Kazuki Tsubokura 1 , 6 , Yoichi Nakao 6 , Almira Kurbangalieva 5 , Hirotaka Onoe 3 , Yasuyoshi Watanabe 3 , 4 , Katsunori Tanaka 1 , 2 , 5 , 7 , *
23 April 2021
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.