Bacterial Amyloids for the Remote Release of Tumor-Targeted Protein Drugs

ESTHER VÁZQUEZ; JOAQUÍN SERAS FRONDOZO; MARIA VIRTUDES CESPEDES; PATRICIA ÁLAMO,; LAURA SÁNCHEZ-GARCIA; ISOLDA CASANOVA,; JULIETA M. SANCHEZ; ALEJANDRO SÁNCHEZ-CHARDI; RAMÓN MANGUES; NAROA SERNA; HECTOR LOPEZ LAGUNA; ANTONIO VILLAVERDE; UGUTZ UNZUETA ,; RITA SALA,; MIREIA PESARRODONA; OLIVIA CANO-GARRIDO; ERIC VOLTA DURAN

Cracovia

Congreso; Eurobiotech 2019; 2019

Targi w Krakowie Ltd

Bacterial inclusion bodies (IBs) are amyloidal protein deposits usually observed inrecombinant bacteria during protein production processes 1. They are composed by anintricate mixture of functional and non-functional forms of the recombinant protein 2,that assemble as mechanically stable sub-micron particles with a porous architecture.The combination of mechanical stability, functionality and size in between micro andnano scales have allowed the identification of interesting applications of IBs in materialsciences, biotechnology and biomedicine 3. Upon local administration in tumor tissues,IBs remain stable and functional, but they slowly release functional protein that showsa potent biological local effect on the tumor 4. When IBs are built by tumor-targetedproteins that self-assemble as functional nanoparticles, IBs become a source of tumortargeted nanoscale oligomers 5 that are slowly released from injection site, deliveredto the blood stream, and finally accumulating in remote target tissues 6,7,8. Uponsubcutaneous implantation, IBs formed by oligomeric, CXCR4-targeted recombinanttoxins slowly deliver cytotoxic nanoparticles that selectively destroy tumoral tissue in amouse model of human, CXCR4+ colorectal cancer. These results instruct how IBs canbe engineered to mimic the functioning of secretory granules from the endocrinesystem to generate smart materials for the targeted, highly precise nanomedicine ofcancer.1 de Marco, A. et al. Bacterial inclusion bodies are industrially exploitableamyloids. FEMS microbiology reviews 43, 53?72, (2018).2 Gonzalez-Montalban, N., Garcia-Fruitos, E. & Villaverde, A. Recombinantprotein solubility - does more mean better? Nature biotechnology 25, 718-720, (2007).3 Rinas, U. et al. Bacterial Inclusion Bodies: Discovering Their Better Half. Trendsin biochemical sciences 42, 726-737, (2017).4 Cespedes, M. V. et al. Bacterial mimetics of endocrine secretory granules asimmobilized in vivo depots for functional protein drugs. Scientific reports 6, 35765,(2016).