Stimulus-responsive nanoscale delivery systems triggered by the enzymes in the tumor microenvironment

The tumor microenvironment is the cellular environment that is also described as the "soil" for supporting tumor growth, proliferation, invasion and metastasis, as well as protecting tumor cells from immunological recognition. Notably, tumor cells can grow much faster than other normal organs and invade surrounding tissues more easily, which results in abnormal expression of enzymes in the tumor microenvironment, including matrix metalloproteinases, cathepsins, phospholipases, oxidoreductases, etc. In opposite, due to the high selectivity and catalytic activity, these enzymes can promote nanoparticles to recognize tumor tissues more accurately, and the more accumulation of drugs at primal tumor sites will enhance therapeutic efficacy with lower systemic toxicity. Therefore, one promising antitumor strategy is to design stimulus-responsive nanoscale delivery systems triggered by the enzymes with the support of various nanocarriers, such as liposomes, micelles and inorganic nanoparticles, etc. In this review, numerous facts were cited to summarize and discuss the typical types of enzyme-stimulus responsive nanoscale delivery systems. More importantly, we also focused on their recent advancements in antitumor therapy, and offered the direction for further studies.