title: Non-amyloidogenic peptide tags for the regulatable self-assembling of protein-only nanoparticles.
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.
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Ugutz
authors.initials: U
authors.lastname: Unzueta
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer-Miralles
authors.forename: Juan
authors.initials: J
authors.lastname: Cedano
authors.forename: Xu
authors.initials: X
authors.lastname: Zikung
authors.forename: Mireia
authors.initials: M
authors.lastname: Pesarrodona
authors.forename: Paolo
authors.initials: P
authors.lastname: Saccardo
authors.forename: Elena
authors.initials: E
authors.lastname: García-Fruitós
authors.forename: Joan
authors.initials: J
authors.lastname: Domingo-Espín
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Kailash C
authors.initials: KC
authors.lastname: Gupta
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.forename: Esther
authors.initials: E
authors.lastname: Vazquez
mesh_terms: D006367:HeLa Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D015202:Protein Engineering; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D010455:Peptides; D011506:Proteins; C015462:polyarginine; C033223:polyhistidine; D006639:Histidine