Antiangiogenic anticancer strategy based on nanoparticulate systems

Abstract

Introduction: Angiogenesis is a process that provides a blood supply for cancer cells. The discovery that the blockade of this blood supply results in the inhibition of cancer cell growth has been applied in cancer treatment. This antiangiogenic strategy is mainly directed at the inhibition of the binding process between proangiogenic growth factors and their receptors or the inhibition of the activity of proteolytic enzymes of the extracellular matrix. The toxicity of some antiangiogenic agents, such as small-molecule inhibitors, and the instability of antiangiogenic proteins require their formulation in an appropriate delivery system. On the other hand, active drug targeting to selective markers expressed on tumor vasculature could improve antiangiogenic treatment.Areas covered: The present review focuses on nanoparticulate systems (nanoparticles, liposomes, polymeric micelles, etc.) because their properties could enable both the targeting of endothelial cells and the efficient delivery of antiangiogenic agents. The most important properties of nanoparticles that influence both processes, such as their size, charge and surface modification, are also discussed. Various examples illustrating the targeting ability of nanoparticles are reported, in particular conjugated nanoparticles targeting VEGF and its receptors, fibroblast growth factor and its receptors, EGFRs, MMPs, tubulin function and so on.Expert opinion: Targeting of nanoparticles (e.g., by tumor-penetrating peptides) allows the co-administration of antiangiogenic and anticancer drugs, facilitates drug penetration into extravascular tumor tissue and improves the therapeutic effect at reduced drug doses.