In vitro studies revealed that in response to the high doses of legumain present in the tumor site, the activated melittin would damage the host Mφs, leading to the formation of DM4‐loaded Exo‐like nanovesicles (DENs), while in a low concentration of legumain (simulating circulation condition), the Mφs remained viable. The gene discussed is LGMN; the disease is neoplasm.