Animal models for analysis of immunological responses to nanomaterials: Challenges and considerations

Adv Drug Deliv Rev. Nov-Dec 2018;136-137:82-96. doi: 10.1016/j.addr.2018.09.012. Epub 2018 Sep 29.


Nanotechnology provides many solutions to improve conventional drug delivery and has a unique niche in the areas related to the specific targeting of the immune system, such as immunotherapies and vaccines. Preclinical studies in this field rely heavily on the combination of in vitro and in vivo methods to assess the safety and efficacy of nanotechnology platforms, nanoparticle-formulated drugs, and vaccines. While certain types of toxicities can be evaluated in vitro and good in vitro-in vivo correlation has been demonstrated for such tests, animal studies are still needed to address complex biological questions and, therefore, provide a unique contribution to establishing nanoparticle safety and efficacy profiles. The genetic, metabolic, mechanistic, and phenotypic diversity of currently available animal models often complicates both the animal choice and the interpretation of the results. This review summarizes current knowledge about differences in the immune system function and immunological responses of animals commonly used in preclinical studies of nanomaterials. We discuss challenges, highlight current gaps, and propose recommendations for animal model selection to streamline preclinical analysis of nanotechnology formulations.

Keywords: Allergy; Anaphylaxis; Animals; Complement; Cytokine storm; Inflammation; MPS; Macrophages; Nanoparticles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Immune System / immunology
  • Immune System / innervation*
  • Models, Animal*
  • Nanostructures / chemistry*
  • Nanotechnology*