Targeting low-density lipoprotein receptors with protein-only nanoparticles
Xu, Zhikun (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Céspedes, María Virtudes (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Unzueta Elorza, Ugutz (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Álamo, Patricia (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Pesarrodona Roches, Mireia (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Mangues, Ramon 1957- (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Vázquez Gómez, Esther, dir. (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Ferrer-Miralles, Neus (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Data:	2015
Resum:	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.
Ajuts:	Instituto de Salud Carlos III FIS/PI12/01861 Ministerio de Economía y Competitividad BIO2013-41019P Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-132
Nota:	We are grateful to the Protein Production Platform (CIBER-BBN-UAB) for helpful technical assistance and for protein production and purification services (http://​www.​ciber-bbn.​es/​en/​programas/​89-plataforma-de-produccion-de-proteinas-ppp). We are indebted to FIS PI12/01861, Marató 416/C/2013-2030 and NanoMets to RM, MINECO BIO2013-41019-P to AV, AGAUR (2014SGR-132), and CIBER de Bioingeniería, Biomateriales y Nanomedicina (project NANOPROTHER) for funding our research on protein-based therapeutics. We thank the CIBER-BBN Nanotoxicology Unit for fluorescent in vivo follow-up using the IVIS equipment. We are also indebted to the Cell Culture and Citometry Units of the Servei de Cultius Cel·lulars, Producció d'Anticossos i Citometria (SCAC), and to the Servei de Microscòpia, both at the UAB, and to the Soft Materials Service (ICMAB-CSIC/CIBER-BBN). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. Z. X. and M. P. acknowledge financial support from China Scholarship Council and Universitat Autònoma de Barcelona through pre-doctoral fellowships, respectively. AV received an ICREA ACADEMIA award.
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Recombinant protein ; Proteïnes recombinants ; Self-assembling ; Auto-ensamblatge ; Nanoparticles ; Nanopartícules ; LDLR ; Cell targeting ; Cel·lules diana ; BBB ; Biomedicine ; Biomedicina
Publicat a:	Journal of nanoparticle research, Vol. 17 issue 3 (March 2015) , article 150, ISSN 1388-0764

DOI: 10.1007/s11051-015-2959-8

Post-print 27 p, 985.0 KB

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