Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles

A single chain polypeptide containing the low density lipoprotein receptor (LDLR) ligand Seq-1 with blood-brain barrier (BBB) crossing activity has been successfully modified by conventional genetic engineering to self-assemble into stable protein-only nanoparticles of 30 nm. The nanoparticulate pre...

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Detalles Bibliográficos
Autores: Serna, Naroa|||0000-0001-5682-8198, Céspedes, María Virtudes|||0000-0003-2956-5833, Saccardo, Paolo|||0000-0002-3092-1404, Xu, Zhikun, Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Álamo, Patricia|||0000-0003-0510-5701, Pesarrodona Roches, Mireia|||0000-0001-9669-8471, Sánchez Chardi, Alejandro|||0000-0002-8789-1883, Roldán, Mónica, Mangues, Ramon|||0000-0003-2661-9525, Vázquez, Esther|||0000-0003-1052-0424, Villaverde, Antonio|||0000-0002-2615-4521, Ferrer-Miralles, Neus|||0000-0003-2981-3913
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:174137
Acceso en línea:https://ddd.uab.cat/record/174137
https://dx.doi.org/urn:doi:10.1016/j.nano.2016.01.004
Access Level:acceso abierto
Palabra clave:Biodistribution
LDLR
Nanoparticles
Protein engineering
Self-assembling
Descripción
Sumario:A single chain polypeptide containing the low density lipoprotein receptor (LDLR) ligand Seq-1 with blood-brain barrier (BBB) crossing activity has been successfully modified by conventional genetic engineering to self-assemble into stable protein-only nanoparticles of 30 nm. The nanoparticulate presentation dramatically enhances in vitro, LDLR-dependent cell penetrability compared to the parental monomeric version, but the assembled protein does not show any enhanced brain targeting upon systemic administration. While the presentation of protein drugs in form of nanoparticles is in general advantageous regarding correct biodistribution, this principle might not apply to brain targeting that is hampered by particular bio-physical barriers. Irrespective of this fact, which is highly relevant to the nanomedicine of central nervous system, engineering the cationic character of defined protein stretches is revealed here as a promising and generic approach to promote the controlled oligomerization of biologically active protein species as still functional, regular nanoparticles.

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