Formulating tumor-homing peptides as regular nanoparticles enhances receptor-mediated cell penetrability
Xu, Zhikun (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Unzueta Elorza, Ugutz (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Roldán, Mónica (Universitat Autònoma de Barcelona. Servei de Microscòpia)
Mangues, Ramon 1957- (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Sánchez Chardi, Alejandro (Universitat Autònoma de Barcelona. Servei de Microscòpia)
Ferrer-Miralles, Neus (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Data:	2015
Resum:	Homing peptides are exploited in nanomedicine to functionalize either free drugs or nanostructured materials used as drug carriers. However, the influence of multivalent versus monovalent peptide presentation on the interaction with the receptor and on the consequent intracellular delivery of the associated cargo remains poorly explored. By using a tumor-homing peptide (T22) with regulatable self-assembling properties we have investigated here if its display in a either a monomeric form or as multimeric, self-assembled protein nanoparticles might determine the efficacy of receptor-mediated penetrability into target cells. This has been monitored by using a fluorescent cargo protein (iRFP), which when fused to the homing peptide acts as convenient reporter. The results indicate that the nanoparticulate protein versions are significantly more efficient in mediating receptor-dependent uptake than their unassembled counterparts. These finding stresses an additional benefit of nanostructured materials based on repetitive building blocks, regarding the multivalent presentation of cell ligands that facilitate cell penetration in drug delivery applications.
Ajuts:	Ministerio de Economía y Competitividad BIO2013-41019P Instituto de Salud Carlos III FIS/PI12/00327 Instituto de Salud Carlos III FIS/PI12/01861
Nota:	The authors acknowledge the financial support granted to E.V. (PI12/00327) and R.M. (PI12/01861) from FIS, to E.V. (TV32013-133930) and to R.M. and A.V. (TV32013-132031) from La Marató de TV3 (416/C/2013), to A.V. from MINECO (Grant BIO2013-41019-P) and from the Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina (NANOPROTHER and NANOCOMETS projects). We are grateful to the Protein Production Platform (CIBER-BBN-UAB) for protein production and purification services (http://www.ciber-bbn.es/en/programas/89-plataforma-de-produccion-de-proteinas-ppp), to the Servei de Cultius Cel·lulars, Producció d׳Anticossos i Citometria (SCAC), to the Servei de Microscòpia, both at the UAB and to the Soft Materials Service (ICMAB-CSIC/CIBER-BBN). Z.X. received a fellowship grant from China Scholarship Council (Grant no. 2011630065) and U.U. from ISCIII. AV received an ICREA ACADEMIA award.
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió sotmesa a revisió
Matèria:	Biomaterials ; Biomimetic ; Biomimètics ; Nanoparticles ; Nanopartícules ; Protein materials ; Materials proteínics
Publicat a:	Materials letters, Vol. 154 (Sept. 2015) , p. 140-143, ISSN 0167-577X

DOI: 10.1016/j.matlet.2015.04.055

Pre-print 7 p, 252.3 KB

Figures 2 p, 310.0 KB

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