ABOUT THE COVER
Delivery of therapeutics to pancreatic ductal adenocarcinomas (PDACs) is challenging due to the physical stromal barriers surrounding these tumors. Lo and colleagues applied tumor-penetrating nanocomplexes (TPNs) to breach the stroma and effectively deliver therapeutic siRNA to PDAC. As depicted on the cover, these particles are self-assembled nanostructures comprised of tandem peptides containing both a tumor-penetrating iRGD domain and a cell-penetrating domain, PEGylated derivatives of these tandem peptides, and siRNA. TPNs delivering anti-Kras siRNA exhibited tumor-penetrating ability in 3D organoids and autochthonous tumors, and slowed PDAC growth in vivo. The modular construction of the TPN platform allows for facile adaptation for future genetic targets.