Design of cathepsin-sensitive linkers for tumor-selective bioconjugate drug delivery.

Cysteine cathepsin, particularly cathepsin B, have emerged as pivotal enzymatic targets in the design of drug delivery systems owing to their overexpression in diverse pathological conditions, most notably cancer. This review provides a comprehensive overview of cathepsin B-cleavable linkers, emphasizing their role in current bioconjugate design and their application across multiple therapeutic platforms. It also provides a comparative overview of linker engineering guided by cathepsin B, ranging from simple dipeptides constructs to modified peptide linkers.