Therefore, NanoTAC can undergo selective enzymatic cleavage to release the active PROTAC and photosensitizer in tumor cells, potentially reducing adverse effects from off-target HK2 proteolysis.53 This notion is supported by molecular binding simulations, which revealed that intact NanoTAC fails to bind either to target HK2 or VHL but exhibits meaningful binding affinities after cleavage into PROTACs (Fig. 1m, Supplementary Figs. 11 and 12). Here, VHL is linked to neoplasm.