Fig. 5. Tumor growth reduction via doxorubicin-based SeCT therapy.

(A) Using the doxo-PE reagent, this application is based on the indiscriminate tagging of cancer cell surface proteins with a doxorubicin moiety. Following internalization, the Val-Cit-PAB linker is designed to be cleaved by overexpressed cathepsin B, leading to drug release and eventual cell death. (B) Cytotoxicity assay against HeLa cells showed that doxo-PE is roughly 100-fold less toxic than its active agent, doxorubicin. (C) Cytotoxicity assay that shows the combination of the SeCT labeling reagents (doxo-PE/GArM) causes significantly higher HeLa cell death compared with the addition of individual reagents (doxo-PE only or GArM only). P values were determined by paired t test. All numerical data are presented as means ± SEM of three replicates. *P < 0.05, **P < 0.01, and ***P < 0.001. IC₅₀, median inhibitory concentration.