proteaseresponsive

Protease-responsive describes materials, probes, or constructs that change properties when exposed to proteases—enzymes that cleave peptide bonds. The concept relies on incorporating protease-cleavable motifs into linkers, polymers, or scaffolds, making activation contingent on the presence or activity of specific proteases. Common proteases exploited include matrix metalloproteinases MMP-2 and MMP-9, cathepsins, and certain caspases, though many serine proteases and others can be targeted with tailored sequences.

Applications include targeted drug delivery, where a therapeutic payload is masked until a protease at the disease site cleaves a linker; in imaging, protease-activatable probes generate signal only after cleavage for improved contrast; in biomaterials, protease-degradable hydrogels or scaffolds enable tissue remodeling by cells by releasing encapsulated factors or altering mechanics.

Design considerations involve selecting protease-specific peptide sequences to achieve desired cleavage, ensuring stability in circulation, controlling kinetics and release profiles, and minimizing off-target activation and immunogenicity.

Limitations include variable protease expression across individuals and tissues, the presence of multiple proteases that may cleave shared motifs, potential premature activation, and challenges in translating to clinical use.

Protease-responsive systems are an active area in biomaterials and nanomedicine, with several preclinical demonstrations and some early-stage clinical investigations.