Proteases are hydrolytic enzymes fundamental for a variety of physiological processes, but the loss of their regulation leads to aberrant functions that promote onset and progression of many diseases including cancer. Proteases have been implicated in almost every hallmark of cancer and whilst widely investigated for tumour therapy, clinical adoption of protease inhibitors as drugs remains a challenge due to issues such as off-target toxicity and inability to achieve therapeutic doses at the disease site. Now, nanotechnology-based solutions and strategies are emerging to circumvent these issues. In this review, preclinical advances in approaches to enhance the delivery of protease drugs and the exploitation of tumour-derived protease activities to promote targeting of nanomedicine formulations is examined. Whilst this field is still in its infancy, innovations to date suggest that nanomedicine approaches to protease targeting or inhibition may hold much therapeutic and diagnostic potential.
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