Structural and functional features of self-assembling protein nanoparticles produced in endotoxin-free Escherichia coli
Creators: name: Rueda, Fabian
name: Céspedes, Maria Virtudes
name: Sánchez-Chardi, Alejandro
name: Seras-Franzoso, Joaquin
name: Pesarrodona, Mireia
name: Ferrer-Miralles, Neus
name: Vázquez, Esther
name: Rinas, Ursula
name: Unzueta, Ugutz
name: Mamat, Uwe
name: Mangues, Ramon
name: García-Fruitós, Elena
name: Villaverde, Antonio
Publisher: name: London : BioMed Central Ltd.
Year: 2016
Subjects: subject: Biodistribution
subject: Biomaterials
subject: E. coli
subject: Endotoxin-free strains
subject: Nanomedicine
subject: Nanoparticles
subject: Protein engineering
subject: Recombinant proteins
subject: chemokine receptor CXCR4
subject: endotoxin
subject: nanoparticle
subject: animal experiment
subject: animal model
subject: animal tissue
subject: Article
subject: bacterial strain
subject: bioaccumulation
subject: colorectal cancer
subject: controlled study
subject: Escherichia coli
subject: in vitro study
subject: in vivo study
subject: mouse
subject: nanofabrication
subject: nonhuman
subject: protein assembly
subject: protein engineering
subject: protein structure
subject: quality control
subject: Dewey Decimal Classification::500 | Naturwissenschaften
subject: Dewey Decimal Classification::500 | Naturwissenschaften::570 | Biowissenschaften, Biologie

description: 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.