Release of targeted protein nanoparticles from functional bacterial amyloids : A death star-like approach
Unzueta Elorza, Ugutz (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Céspedes, María Virtudes (Institut d'Investigació Biomèdica Sant Pau)
Sala, Rita (Institut d'Investigació Biomèdica Sant Pau)
Álamo, Patricia (Institut d'Investigació Biomèdica Sant Pau)
Sánchez Chardi, Alejandro (Universitat Autònoma de Barcelona. Servei de Microscòpia)
Pesarrodona Roches, Mireia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Sánchez-García, Laura (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Cano-Garrido, Olivia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Mangues, Ramon 1957- (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Seras-Franzoso, Joaquin (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2018
Abstract:	Sustained release of drug delivery systems (DDS) has the capacity to increase cancer treatment efficiency in terms of drug dosage reduction and subsequent decrease of deleterious side effects. In this regard, many biomaterials are being investigated but none offers morphometric and functional plasticity and versatility comparable to protein-based nanoparticles (pNPs). Here we describe a new DDS by which pNPs are fabricated as bacterial inclusion bodies (IB), that can be easily isolated, subcutaneously injected and used as reservoirs for the sustained release of targeted pNPs. Our approach combines the high performance of pNP, regarding specific cell targeting and biodistribution with the IB supramolecular organization, stability and cost effectiveness. This renders a platform able to provide a sustained source of CXCR4-targeted pNPs that selectively accumulate in tumor cells in a CXCR4 colorectal cancer xenograft model. In addition, the proposed system could be potentially adapted to any other protein construct offering a plethora of possible new therapeutic applications in nanomedicine.
Grants:	Ministerio de Ciencia e Innovación BIO2016-76063-R Instituto de Salud Carlos III PI15/00272 Instituto de Salud Carlos III PI15/00378 Instituto de Salud Carlos III PIE15/00028 Instituto de Salud Carlos III 2017FI_B100063 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/PROD 00055
Note:	Altres ajuts: we are indebted to CIBER de Bioingeniería, Biomateriales y Nanomedicina (projects NANOREMOTE and VENOM4CANCER) to EV and AV respectively, Marató de TV3 foundation (TV32013-132031) and CIBER (NanoMets3) to RM. Protein production has been partially performed by the ICTS "NANBIOSIS", more specifically by the Protein Production Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)/IBB, at the UAB SepBioES scientific-technical service (http://www.nanbiosis.es/unit/u1-protein-production-platform-ppp/), whereas the in vivo biodistribution assays were performed in the NANBIOSIS Nanotoxicology platform (http://www.nanbiosis.es/unit/u18-nanotoxicology-unit/). We are also indebted to Fran Cortes from the Cell Culture and Cytometry Units of the Servei de Cultius Cel·lulars, Producció d'Anticossos i Citometria (SCAC), and to the Servei de Microscòpia at the UAB. AV received an ICREA ACADEMIA award. U.U received a Sara Borrell postdoctoral fellowship from ISCIII, MVC was supported by Miguel Servet contract from ISCIII, and JSF received and AECC postdoctoral fellowship.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Colorectal cancer ; Drug delivery system ; Inclusion bodies ; Supramolecular organizations ; Sustained release ; Targeted proteins ; Therapeutic Application ; Treatment efficiency ; Amyloid ; Animals ; Bacteria ; Colorectal Neoplasms ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Female ; Humans ; Inclusion Bodies ; Mice ; Mice, Nude ; Nanoparticles ; Proteins ; Receptors, CXCR4 ; Tissue Distribution ; Xenograft Model Antitumor Assays
Published in:	Journal of Controlled Release, Vol. 279 (June 2018) , p. 29-39, ISSN 1873-4995

DOI: 10.1016/j.jconrel.2018.04.004

Postprint 32 p, 1.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles