Peptides for cell-selective drug delivery.

The ability to target specific cell types to achieve optimal distribution of therapeutic entities into diseased tissues, while limiting possible adverse off-target effects, has long been a goal of many research groups and pharmaceutical organizations. This review focuses on peptidic tissue-specific biomarkers that allow peptides to act as homing devices for specific tissue types or organs, with a focus on homing peptides (HPs) and cell-penetrating homing peptides (CPHPs). These HPs, in addition to promoting cellular uptake, can deliver a variety of cargos (drugs, oligonucleotides and nanoparticles) into cells. Two such peptides that have entered clinical trials are the tumor-homing peptide asparagine-glycine-arginine (NGR) (fused to human tumor necrosis factor), which selectively binds CD13, an aminopeptidase that is overexpressed on tumor blood vessels, and cyclo[Arg-Gly-Asp-D-Phe-(NMeVal)] (cRGD, cilengitide), an anti-angiogenic agent that targets the α(v)β(3) and α(v)β(5) integrins.