Enzyme-responsive nanocarriers hold great promises for precision delivery of therapeutics. Silica nanocarriers and liposomes functionalized with protease-cleavable peptide linkers (e.g., cathepsin B-cleavable peptide) have emerged as powerful platforms for selectively releasing therapeutic payloads within tumor microenvironments. This review presents recent advances in cathepsin B-responsive systems, emphasizing design principles such as peptide-linker selection, nanoparticle engineering, and incorporation into antibody-drug conjugates. We also address persisting challenges in clinical translation, including enzyme expression variability and linker stability in order to discuss strategies to overcome these barriers through advanced bioengineering approaches.
Iqbal et al. (Thu,) studied this question.