Structural and functional features of self-assembling protein nanoparticles produced in endotoxin-free Escherichia coli
Rueda, Fabian (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Céspedes, María Virtudes (Institut d'Investigació Biomèdica Sant Pau)
Sánchez Chardi, Alejandro (Universitat Autònoma de Barcelona. Servei de Microscòpia)
Seras-Franzoso, Joaquin (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Pesarrodona Roches, Mireia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ferrer-Miralles, Neus (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Rinas, Ursula (Helmholtz Centre for Infection Research)
Unzueta Elorza, Ugutz (Institut d'Investigació Biomèdica Sant Pau)
Mamat, Uwe (Airway Research Center North)
Mangues, Ramon 1957- (Institut d'Investigació Biomèdica Sant Pau)
Garcia-Fruitos, Elena (Institut de Recerca i Tecnologia Agroalimentàries)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Universitat Autònoma de Barcelona

Date:	2016
Abstract:	Background: production of recombinant drugs in process-friendly endotoxin-free bacterial factories targets to a lessened complexity of the purification process combined with minimized biological hazards during product application. The development of nanostructured recombinant materials in innovative nanomedical activities expands such a need beyond plain functional polypeptides to complex protein assemblies. While Escherichia coli has been recently modified for the production of endotoxin-free proteins, no data has been so far recorded regarding how the system performs in the fabrication of smart nanostructured materials. - Results: we have here explored the nanoarchitecture and in vitro and in vivo functionalities of CXCR4-targeted, self-assembling protein nanoparticles intended for intracellular delivery of drugs and imaging agents in colorectal cancer. Interestingly, endotoxin-free materials exhibit a distinguishable architecture and altered size and target cell penetrability than counterparts produced in conventional E. coli strains. These variant nanoparticles show an eventual proper biodistribution and highly specific and exclusive accumulation in tumor upon administration in colorectal cancer mice models, indicating a convenient display and function of the tumor homing peptides and high particle stability under physiological conditions. - Discussion: the observations made here support the emerging endotoxin-free E. coli system as a robust protein material producer but are also indicative of a particular conformational status and organization of either building blocks or oligomers. This appears to be promoted by multifactorial stress-inducing conditions upon engineering of the E. coli cell envelope, which impacts on the protein quality control of the cell factory.
Grants:	Instituto de Salud Carlos III PI12/00327 Ministerio de Economía y Competitividad BIO2013-41019-P Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-132
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Protein engineering ; Recombinant proteins ; Nanoparticles ; Nanomedicine ; Biomaterials ; Biodistribution ; E. coli ; Endotoxin-free strains
Published in:	Microbial cell factories, Vol. 15 (2016) , art. 59, ISSN 1475-2859

DOI: 10.1186/s12934-016-0457-z
PMID: 27059706

12 p, 3.2 MB

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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