Tumor-penetrating peptides: a shift from magic bullets to magic guns.

The targeted delivery of drugs and imaging agents to tumor vessels is an attractive strategy to enhance anticancer therapy and tumor detection, but such targeting does not mean efficient distribution into the tumor. Two consecutive papers, one in Cancer Cell and one in Science, report that a single peptide has the potential to selectively deliver a large variety of therapeutic agents and diagnostics to a tumor site and then to ensure their distribution deep in the tumor parenchyma. This peptide has the capacity to bind specific alpha(V) integrins through an arginine-glycine-aspartate motif and, after local proteolysis reveals a cryptic arginine/lysine-X-X-arginine/lysine motif, to bind the neuropilin-1 receptor and thereby increase tumor vascular permeability. Remarkably, this penetrating peptide works not only when it is conjugated to the payload, but also when it is coadministered with small molecules, nanoparticles, or monoclonal antibodies.