title: Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles.
abstract: 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 30nm. 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.
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Naroa
authors.initials: N
authors.lastname: Serna
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain; Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau (IIB-SantPau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Paolo
authors.initials: P
authors.lastname: Saccardo
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Xu
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain; Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau (IIB-SantPau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Ugutz
authors.initials: U
authors.lastname: Unzueta
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain; Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau (IIB-SantPau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Álamo
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Pesarrodona
authors.affiliation: Servei de Microscòpia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sánchez-Chardi
authors.affiliation: Servei de Microscòpia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Roldán
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain; Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau (IIB-SantPau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Vázquez
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain. Electronic address: antoni.villaverde@uab.cat.
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain. Electronic address: neus.ferrer@uab.cat.
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer-Miralles
mesh_terms: D001812:Blood-Brain Barrier; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles; D010455:Peptides; D011973:Receptors, LDL; D014018:Tissue Distribution
chemical_list: C573412:LDLR protein, human; D010455:Peptides; D011973:Receptors, LDL
keywords: Biodistribution; LDLR; Nanoparticles; Protein engineering; Self-assembling