Proteolytic Unlocking of Ultrastable Twin-Acylhydrazone Linkers for Lysosomal Acid-Triggered Release of Anticancer Drugs

Targeted prodrugs exploiting cleavable linkers capable of responding to endogenous stimuli have increasingly been explored for cancer therapy. Successful application of these prodrug designs relies on the manipulation of both stability and responsiveness of the cleavable linkers, which, however, are difficult to be finely regulated, particularly for acid-responsive acylhydrazone bonds. Here we developed a new class of peptide-bridged...