Rational engineering of single-chain polypeptides into protein-only, BBB-targeted nanoparticles
Por:
Serna, N, Cespedes, MV, Saccardo, P, Xu, ZK, Unzueta, U, Alamo, P, Pesarrodona, M, Sanchez-Chardi, A, Roldan, M, Mangues, R, Vazquez, E, Villaverde, A, Ferrer-Miralles, N
Publicada:
1 jul 2016
Resumen:
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. (C) 2016 Elsevier Inc. All rights reserved.
Filiaciones:
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona, Spain
Cespedes, MV:
CIBER BBN, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Oncogenesis & Antitumor Drug Grp, Barcelona, Spain
Saccardo, P:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona, Spain
Xu, ZK:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona, Spain
Unzueta, U:
CIBER BBN, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Oncogenesis & Antitumor Drug Grp, Barcelona, Spain
Alamo, P:
CIBER BBN, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Oncogenesis & Antitumor Drug Grp, Barcelona, Spain
Pesarrodona, M:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona, Spain
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, E-08193 Barcelona, Spain
Roldan, M:
Univ Autonoma Barcelona, Serv Microscopia, E-08193 Barcelona, Spain
Mangues, R:
CIBER BBN, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Oncogenesis & Antitumor Drug Grp, Barcelona, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona, Spain
Ferrer-Miralles, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona, Spain
Green Accepted
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