In vivo architectonic stability of fully de novo designed protein-only nanoparticles

María Virtudes Céspedes, Ugutz Unzueta, Witold Tatkiewicz, Alejandro Sánchez-Chardi, Oscar Conchillo-Solé, Patricia Álamo, Zhikun Xu, Isolda Casanova, José Luis Corchero, Mireia Pesarrodona, Juan Cedano, Xavier Daura, Imma Ratera, Jaume Veciana, Neus Ferrer-Miralles, Esther Vazquez, Antonio Villaverde, Ramón Mangues

Research output: Contribution to journalArticleResearchpeer-review

80 Citations (Web of Science)


The fully de novo design of protein building blocks for self-Assembling as functional nanoparticles is a challenging task in emerging nanomedicines, which urgently demand novel, versatile, and biologically safe vehicles for imaging, drug delivery, and gene therapy. While the use of viruses and virus-like particles is limited by severe constraints, the generation of protein-only nanocarriers is progressively reachable by the engineering of protein-protein interactions, resulting in self-Assembling functional building blocks. In particular, end-terminal cationic peptides drive the organization of structurally diverse protein species as regular nanosized oligomers, offering promise in the rational engineering of protein self-Assembling. However, the in vivo stability of these constructs, being a critical issue for their medical applicability, needs to be assessed. We have explored here if the cross-molecular contacts between protein monomers, generated by end-terminal cationic peptides and oligohistidine tags, are stable enough for the resulting nanoparticles to overcome biological barriers in assembled form. The analyses of renal clearance and biodistribution of several tagged modular proteins reveal long-term architectonic stability, allowing systemic circulation and tissue targeting in form of nanoparticulate material. This observation fully supports the value of the engineered of protein building blocks addressed to the biofabrication of smart, robust, and multifunctional nanoparticles with medical applicability that mimic structure and functional capabilities of viral capsids. © 2014 American Chemical Society.
Original languageEnglish
Pages (from-to)4166-4176
JournalACS Nano
Publication statusPublished - 27 May 2014


  • architectonic stability
  • artificial viruses
  • biodistribution
  • building blocks
  • drug delivery
  • genetic engineering
  • nanoparticles
  • protein folding
  • protein nanoparticles
  • self-Assembling
  • targeting


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