Non-amyloidogenic peptide tags for the regulatable self-assembling of protein-only nanoparticles.

Ugutz Unzueta, Neus Ferrer-Miralles, Juan Cedano, Xu Zikung, Mireia Pesarrodona, Paolo Saccardo, Elena García-Fruitós, Joan Domingo-Espín, Pradeep Kumar, Kailash C Gupta, Ramón Mangues, Antonio Villaverde, Esther Vazquez

Index: Biomaterials 33(33) , 8714-22, (2012)

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Abstract

Controlling the self-assembling of building blocks as nanoscale entities is a requisite for the generation of bio-inspired vehicles for nanomedicines. A wide spectrum of functional peptides has been incorporated to different types of nanoparticles for the delivery of conventional drugs and nucleic acids, enabling receptor-specific cell binding and internalization, endosomal escape, cytosolic trafficking, nuclear targeting and DNA condensation. However, the development of architectonic tags to induce the self-assembling of functionalized monomers has been essentially neglected. We have examined here the nanoscale architectonic capabilities of arginine-rich cationic peptides, that when displayed on His-tagged proteins, promote their self-assembling as monodisperse, protein-only nanoparticles. The scrutiny of the cross-molecular interactivity cooperatively conferred by poly-arginines and poly-histidines has identified regulatable electrostatic interactions between building blocks that can also be engineered to encapsulate cargo DNA. The combined use of cationic peptides and poly-histidine tags offers an unusually versatile approach for the tailored design and biofabrication of protein-based nano-therapeutics, beyond the more limited spectrum of possibilities so far offered by self-assembling amyloidogenic peptides.Copyright © 2012 Elsevier Ltd. All rights reserved.