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

• Published in: Nanomedicine Vol. 8; no. 8; pp. 1263 - 1266
• Main Authors: Domingo-Espín, Joan, MSc, Petegnief, Valérie, PhD, de Vera, Núria, MD, PhD, Conchillo-Solé, Oscar, MSc, Saccardo, Paolo, MSc, Unzueta, Ugutz, MSc, Vazquez, Esther, MD, PhD, Cedano, Juan, PhD, Negro, Luciana, BSc, Daura, Xavier, PhD, Peluffo, Hugo, PhD, Planas, Anna M., PhD, Villaverde, Antonio, PhD, Ferrer-Miralles, Neus, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2012
• Subjects: Binding Sites; Biomaterials; Cell Differentiation; Cell Proliferation; Differentiation; Drug delivery; Drug Delivery Systems; Extracellular signal-regulated kinase; Humans; Integrins; Integrins - chemistry; Integrins - metabolism; Internal Medicine; Ligands; MAP Kinase Signaling System; nanoparticles; Nanoparticles - chemistry; nanotechnology; Neurons; Neurons - cytology; Neurons - metabolism; Oligopeptides - chemistry; Peptides - chemistry; Pheochromocytoma cells; Protein Binding; Protein nanoparticles; RGD; Signal Transduction; Trophic factors; Protein nanoparticles; Neurons; RGD; Integrins; Biomaterials
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2012.06.005

Abstract 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. From the Clinical Editor This work focuses on RGD peptides, which are among the most commonly used tags for targeted drug delivery. They also promote protoneurite formation and expression of neuronal markers (MAP2) in model PC12 cells, which is an unexpected but relevant event in the functionalization of drugs and their nanocarriers.