We then evaluated whether the newly developed HTE phosphotriester protecting groups on 3 are cleaved by carboxylesterase‐1 (CES1), an enzyme expressed at elevated levels in cells with high metabolic activity such as liver cells, monocytes, macrophages, lung cells and is even overexpressed in certain types of cancer cells such as gallbladder and liver cancer.[25, 26, 27] For the experiment, 3 was treated with the purified CES1 enzyme and the reaction was monitored by HPLC (Figure 2A). Here, CES1 is linked to liver cancer.