Targeting low-density lipoprotein receptors with protein-only nanoparticles
Por:
Xu Z., Céspedes M.V., Unzueta U., Álamo P., Pesarrodona M., Mangues R., Vázquez E., Villaverde A., Ferrer-Miralles N.
Publicada:
1 ene 2015
Resumen:
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. © 2015, Springer Science+Business Media Dordrecht.
Filiaciones:
Xu Z.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Céspedes M.V.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau (IIB-SantPau), Hospital de la Santa Creu i Sant Pau, C/Sant Antoni Maria Claret, 167, Barcelona, 08025, Spain
Unzueta U.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Álamo P.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau (IIB-SantPau), Hospital de la Santa Creu i Sant Pau, C/Sant Antoni Maria Claret, 167, Barcelona, 08025, Spain
Pesarrodona M.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Mangues R.:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau (IIB-SantPau), Hospital de la Santa Creu i Sant Pau, C/Sant Antoni Maria Claret, 167, Barcelona, 08025, Spain
Vázquez E.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Villaverde A.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
Ferrer-Miralles N.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain
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