TY - JOUR
T1 - Targeting low-density lipoprotein receptors with protein-only nanoparticles
AU - Xu, Zhikun
AU - Céspedes, María Virtudes
AU - Unzueta, Ugutz
AU - Álamo, Patricia
AU - Pesarrodona, Mireia
AU - Mangues, Ramón
AU - Vázquez, Esther
AU - Villaverde, Antonio
AU - Ferrer-Miralles, Neus
PY - 2015/1/1
Y1 - 2015/1/1
N2 - © 2015, Springer Science+Business Media Dordrecht. Low-density lipoprotein receptors (LDLR) are appealing cell surface targets in drug delivery, as they are expressed in the blood–brain barrier (BBB) endothelium and are able to mediate transcytosis of functionalized drugs for molecular therapies of the central nervous system (CNS). On the other hand, brain-targeted drug delivery is currently limited, among others, by the poor availability of biocompatible vehicles, as most of the nanoparticles under development as drug carriers pose severe toxicity issues. In this context, protein nanoparticles offer functional versatility, easy and cost-effective bioproduction, and full biocompatibility. In this study, we have designed and characterized several chimerical proteins containing different LDLR ligands, regarding their ability to bind and internalize target cells and to self-organize as viral mimetic nanoparticles of about 18 nm in diameter. While the self-assembling of LDLR-binding proteins as nanoparticles positively influences cell penetration in vitro, the nanoparticulate architecture might be not favoring BBB crossing in vivo. These findings are discussed in the context of the use of nanostructured materials as vehicles for the systemic treatment of CNS diseases.
AB - © 2015, Springer Science+Business Media Dordrecht. Low-density lipoprotein receptors (LDLR) are appealing cell surface targets in drug delivery, as they are expressed in the blood–brain barrier (BBB) endothelium and are able to mediate transcytosis of functionalized drugs for molecular therapies of the central nervous system (CNS). On the other hand, brain-targeted drug delivery is currently limited, among others, by the poor availability of biocompatible vehicles, as most of the nanoparticles under development as drug carriers pose severe toxicity issues. In this context, protein nanoparticles offer functional versatility, easy and cost-effective bioproduction, and full biocompatibility. In this study, we have designed and characterized several chimerical proteins containing different LDLR ligands, regarding their ability to bind and internalize target cells and to self-organize as viral mimetic nanoparticles of about 18 nm in diameter. While the self-assembling of LDLR-binding proteins as nanoparticles positively influences cell penetration in vitro, the nanoparticulate architecture might be not favoring BBB crossing in vivo. These findings are discussed in the context of the use of nanostructured materials as vehicles for the systemic treatment of CNS diseases.
KW - BBB
KW - Biomedicine
KW - Cell targeting
KW - Nanoparticles, LDLR
KW - Recombinant protein
KW - Self-assembling
U2 - https://doi.org/10.1007/s11051-015-2959-8
DO - https://doi.org/10.1007/s11051-015-2959-8
M3 - Article
VL - 17
JO - Journal of Nanoparticle Research
JF - Journal of Nanoparticle Research
SN - 1388-0764
ER -