Short Communication RGD-based cell ligands for cell-targeted drug delivery act as potent trophic factors

Integrin-binding, Arg-Gly-Asp (RGD)–containing peptides are the most widely used agents to deliver drugs, nanoparticles, and imaging agents. Although in nature, several protein-mediated signal transduction events depend on RGD motifs, the potential of RGD-empowered materials in triggering undesired cell-signaling cascades has been neglected. Using an RGD-functionalized protein nanoparticle, we show here that the RGD motif acts as a powerful trophic factor, supporting extracellular signal–regulated kinase 1/2 (ERK1/2)–linked cell proliferation and partial differentiation of PC12 cells, a neuronlike model.