To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery

Because of the particular characteristics of the tumor microenvironment and tumor angiogenesis, it is possible to design drug delivery systems that specifically target anti-cancer drugs to tumors. Most of the conventional chemotherapeutic agents have poor pharmacokinetics profiles and are distributed non-specifically in the body leading to systemic toxicity associated with serious side effects. Therefore, the development of drug delivery systems able to target the tumor site is becoming a real challenge that is currently addressed. Nanomedicine can reach tumor passively through the leaky vasculature surrounding the tumors by the Enhanced Permeability and Retention effect whereas ligands grafted at the surface of nanocarriers allow active targeting by binding to the receptors overexpressed by cancer cells or angiogenic endothelial cells. This review is divided into two parts: the first one describes the tumor microenvironment and the second one focuses on the exploitation and the understanding of these characteristics to design new drug delivery systems targeting the tumor. Delivery of conventional chemotherapeutic anti-cancer drugs is mainly discussed.