Unzueta, Ugutz; Ferrer-Miralles, Neus; Cedano, Juan; Xu Zikung; Pesarrodona, Mireia; Saccardo, Paolo; Garcia-Fruitos, Elena; Domingo-Espin, Joan; Kumar, Pradeep; Gupta, Kailash C.; Mangues, Ramon; Villaverde, Antonio; Vazquez, Esther
Non-amyloidogenic peptide tags for the regulatable self-assembling of protein-only nanoparticles
BIOMATERIALS, 33:8714-8722, NOV 2012

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. (C) 2012 Elsevier Ltd. All rights reserved.

DOI:10.1016/j.biomaterials.2012.08.033

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