Structural and functional features of self-assembling protein nanoparticles produced in endotoxin-free Escherichia coli

authored by

Fabián Rueda, María Virtudes Céspedes, Alejandro Sánchez-Chardi, Joaquin Seras-Franzoso, Mireia Pesarrodona, Neus Ferrer-Miralles, Esther Vázquez, Ursula Rinas, Ugutz Unzueta, Uwe Mamat, Ramón Mangues, Elena García-Fruitós, Antonio Villaverde

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.

Organisation(s)

Institute of Technical Chemistry

External Organisation(s)

Autonomous University of Barcelona (UAB)
Centros de Investigacion Biomedica en Red - CIBER
Helmholtz Centre for Infection Research (HZI)
Research Center Borstel - Leibniz Lung Center
IRTA - Institute of Agrifood Research and Technology

Type

Article

Journal

Microbial cell factories

Volume

15

ISSN

1475-2859

Publication date

08.04.2016

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Biotechnology, Bioengineering, Applied Microbiology and Biotechnology

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1186/s12934-016-0457-z (Access: Open)