Targeting tumor associated macrophages: The new challenge for nanomedicine.

The engineering of new nanomedicines with ability to target and kill or re-educate Tumor Associated Macrophages (TAMs) stands up as a promising strategy to induce the effective switching of the tumor-promoting immune suppressive microenvironment, characteristic of tumors rich in macrophages, to one that kills tumor cells, is anti-angiogenic and promotes adaptive immune responses. Alternatively, the loading of monocytes/macrophages in blood circulation with nanomedicines, may be used to profit from the high infiltration ability of myeloid cells and to allow the drug release in the bulk of the tumor. In addition, the development of TAM-targeted imaging nanostructures, can be used to study the macrophage content in solid tumors and, hence, for a better diagnosis and prognosis of cancer disease. The major challenges for the effective targeting of TAM with nanomedicines and their application in the clinic have already been identified. These challenges are associated to the undesirable clearance of nanomedicines by, the mononuclear phagocyte system (macrophages) in competing organs (liver, lung or spleen), upon their intravenous injection; and also to the difficult penetration of nanomedicines across solid tumors due to the abnormal vasculature and the excessive extracellular matrix present in stromal tumors. In this review we describe the recent nanotechnology-base strategies that have been developed to target macrophages in tumors.