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

Naroa Serna; María Virtudes Céspedes; Paolo Saccardo; Zhikun Xu; Ugutz Unzueta; Patricia Álamo; Mireia Pesarrodona; Alejandro Sánchez-Chardi; Mónica Roldán; Ramón Mangues; Esther Vázquez; Antonio Villaverde; Neus Ferrer-Miralles

doi:https://doi.org/10.1016/j.nano.2016.01.004

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

Naroa Serna, María Virtudes Céspedes, Paolo Saccardo, Zhikun Xu, Ugutz Unzueta, Patricia Álamo, Mireia Pesarrodona, Alejandro Sánchez-Chardi, Mónica Roldán, Ramón Mangues, Esther Vázquez, Antonio Villaverde, Neus Ferrer-Miralles

Research output: Contribution to journal › Article › Research › peer-review

25 Citations (Scopus)

Abstract

© 2016 Elsevier Inc. 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.

Original language	English
Pages (from-to)	1241-1251
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	12
DOIs	https://doi.org/10.1016/j.nano.2016.01.004
Publication status	Published - 1 Jul 2016

Keywords

Biodistribution
LDLR
Nanoparticles
Protein engineering
Self-assembling

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Serna, N., Céspedes, M. V., Saccardo, P., Xu, Z., Unzueta, U., Álamo, P., Pesarrodona, M., Sánchez-Chardi, A., Roldán, M., Mangues, R., Vázquez, E., Villaverde, A., & Ferrer-Miralles, N. (2016). Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles. Nanomedicine: Nanotechnology, Biology, and Medicine, 12, 1241-1251. https://doi.org/10.1016/j.nano.2016.01.004

@article{eb133a9481c64301a63c5bae569ab0ba,

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

abstract = "{\textcopyright} 2016 Elsevier Inc. 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.",

keywords = "Biodistribution, LDLR, Nanoparticles, Protein engineering, Self-assembling",

author = "Naroa Serna and C{\'e}spedes, {Mar{\'i}a Virtudes} and Paolo Saccardo and Zhikun Xu and Ugutz Unzueta and Patricia {\'A}lamo and Mireia Pesarrodona and Alejandro S{\'a}nchez-Chardi and M{\'o}nica Rold{\'a}n and Ram{\'o}n Mangues and Esther V{\'a}zquez and Antonio Villaverde and Neus Ferrer-Miralles",

year = "2016",

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doi = "https://doi.org/10.1016/j.nano.2016.01.004",

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Serna, N, Céspedes, MV, Saccardo, P, Xu, Z, Unzueta, U, Álamo, P, Pesarrodona, M, Sánchez-Chardi, A, Roldán, M, Mangues, R, Vázquez, E , Villaverde, A & Ferrer-Miralles, N 2016, 'Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 12, pp. 1241-1251. https://doi.org/10.1016/j.nano.2016.01.004

TY - JOUR

T1 - Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles

AU - Serna, Naroa

AU - Céspedes, María Virtudes

AU - Saccardo, Paolo

AU - Xu, Zhikun

AU - Unzueta, Ugutz

AU - Álamo, Patricia

AU - Pesarrodona, Mireia

AU - Sánchez-Chardi, Alejandro

AU - Roldán, Mónica

AU - Mangues, Ramón

AU - Vázquez, Esther

AU - Villaverde, Antonio

AU - Ferrer-Miralles, Neus

PY - 2016/7/1

Y1 - 2016/7/1

N2 - © 2016 Elsevier Inc. 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.

AB - © 2016 Elsevier Inc. 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.

KW - Biodistribution

KW - LDLR

KW - Nanoparticles

KW - Protein engineering

KW - Self-assembling

U2 - https://doi.org/10.1016/j.nano.2016.01.004

DO - https://doi.org/10.1016/j.nano.2016.01.004

M3 - Article

VL - 12

SP - 1241

EP - 1251

ER -

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

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Keywords

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