Exploring therapeutic and diagnostic potential of cysteine cathepsin as targets for cancer therapy with nanomedicine

Cysteine cathepsins have been discovered to be substantially expressed in multiple types of cancer. They play a key role in the progression and growth of these cancers, rendering them appealing targets for nanoscale delivery and noninvasive diagnostic imaging. This review explores cathepsins from the papain-like enzyme family (C1) within the cysteine peptidase clan (CA), emphasizing the role of cathepsin-responsive nanoparticles in tumor growth. Furthermore, it also explores how nanotechnology can harness cathepsin activity to enable targeted drug delivery, improve tumor imaging, and reduce systemic toxicity. By examining the molecular mechanisms governing cathepsin function and evaluating different nanocarrier systems, this work aims to enhance our understanding of targeted cancer treatment. Despite significant advances, challenges remain in translating these nanomedicine platforms into clinical use, including improving delivery efficiency, biocompatibility, long-term safety, and addressing issues such as interspecies protease variability and scalable nanomanufacturing. Future advancement, integrating advanced biomaterials, patient-derived organoid models, bispecific immune-protease targeting, CRISPR-based cathepsin editing, and artificial intelligence-driven pharmacokinetic modeling and analysis will be critical to fully realizing the clinical potential of cathepsin targeted nanomedicines. These innovations hold promises for advancing precision oncology by overcoming current limitations and improving patient outcomes.