Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin‐Targeted Conjugate

This work takes advantage of one of the hallmarks of cancer, that is, the presence of tumor infiltrating cells of the immune system and leukocyte‐secreted enzymes, to promote the activation of an anticancer drug at the tumor site. The peptidomimetic integrin ligand cyclo(DKP‐RGD) was found to accumulate on the surface of αvβ3 integrin‐expressing human renal cell carcinoma 786‐O cells. The ligand was conjugated to the anticancer drug paclitaxel through a Asn‐Pro‐Val (NPV) tripeptide linker, which is a substrate of neutrophil‐secreted elastase. In vitro linker cleavage assays and cell antiproliferative experiments demonstrate the efficacy of this tumor‐targeting conjugate, opening the way to potential therapeutic applications. Exploiting inflammation in cancer: A RGD‐drug conjugate accumulates on the surface of integrin‐expressing human renal cell carcinoma cells and releases paclitaxel upon linker cleavage mediated by neutrophil‐secreted elastase.