Nanostructured recombinant cytokines: A highly stable alternative to short-lived prophylactics

Biomaterials. 2016 Nov;107:102-14. doi: 10.1016/j.biomaterials.2016.08.043. Epub 2016 Aug 27.

Abstract

Cytokines have been widely used as adjuvants and therapeutic agents in treatments of human diseases. Despite their recognized potential as drugs, the medical use of cytokines has considerable drawbacks, mainly related to their low stability and short half-life. Such intrinsic limitations imply the administration of high doses, often prompting toxicity, undesirable side effects and greater production costs. Here, we describe a new category of mechanically stable nanostructured cytokines (TNFα and CCL4/MIP-1β) that resist harsh physicochemical conditions in vitro (pH and temperature), while maintaining functionality. These bio-functional materials are produced in recombinant cell factories through cost-effective and fully scalable processes. Notably, we demonstrate their prophylactic potential in vivo showing they protect zebrafish from a lethal infection by Pseudomonas aeruginosa.

Keywords: Cytokines; Immunization; Inclusion bodies; Macrophages; Nanoparticles; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL4 / administration & dosage*
  • Chemokine CCL4 / chemistry
  • Cytokines / administration & dosage
  • Cytokines / chemistry
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Kinetics
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry
  • Protein Engineering / methods*
  • Pseudomonas Infections / immunology
  • Pseudomonas Infections / pathology
  • Pseudomonas Infections / prevention & control*
  • Recombinant Proteins / adverse effects*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / administration & dosage*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Zebrafish

Substances

  • Chemokine CCL4
  • Cytokines
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha