Cancer-specific ligand-receptor interactions

The concept of cancer targeting, which exploits the abundance of specific molecular epitopes on cancer cells, has been proposed as a strategy to enhance the efficacy and specificity of cancer therapy and diagnostics. Although many promising results have been obtained with this approach, the research experience of the last decades demonstrates clearly the challenges that the clinical application of cancer-targeted approaches faces. This can be attributed to both the complexity of targeted probe-cell interactions as well as the multitude of additional factors, which influence the efficacy of the targeting process. The aim of this chapter is to address the key steps involved in the cellular pathway of ligand-functionalized probes for cancer targeting. Special attention is given to nanoparticulate delivery systems as the most commonly exploited formulations for cancer targeting. Their interaction with target cells is initiated by ligand binding to the cell surface receptor, which is frequently followed by endocytosis of ligand-receptor complex and, in the final phase, by lysosomal degradation. All the aforementioned processes are presented in view of the pathophysiological and molecular features of the biological system as well as the physicochemical and biological properties of targeted probes. Importantly, we discuss the implications of these intracellular events for the therapeutic activity and diagnostic capabilities of targeted agents.