Perspective | Published:

Roadmap and strategy for overcoming infusion reactions to nanomedicines

Nature Nanotechnologyvolume 13pages11001108 (2018) | Download Citation


Infusion reactions (IRs) are complex, immune-mediated side effects that mainly occur within minutes to hours of receiving a therapeutic dose of intravenously administered pharmaceutical products. These products are diverse and include both traditional pharmaceuticals (for example biological agents and small molecules) and new ones (for example nanotechnology-based products). Although IRs are not unique to nanomedicines, they represent a hurdle for the translation of nanotechnology-based drug products. This Perspective offers a big picture of the pharmaceutical field and examines current understanding of mechanisms responsible for IRs to nanomedicines. We outline outstanding questions, review currently available experimental evidence to provide some answers and highlight the gaps. We review advantages and limitations of the in vitro tests and animal models used for studying IRs to nanomedicines. Finally, we propose a roadmap to improve current understanding, and we recommend a strategy for overcoming the problem.

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The study was supported in part (M.A.D.) by federal funds from the National Cancer Institute, National Institutes of Health (NIH), under contract HHSN261200800001E, and by NIH grants CA194058 (D.S.) and EB022040 (D.S.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. J.S. acknowledges support by the European Union Seventh Framework Program grants NMP-2012-309820 (NanoAthero) and NMP-2013-602923 (TheraGlio), and by the Applied Materials and Nanotechnology Center of Excellence at Miskolc University, Hungary. Y.B. acknowledges the partial support of the Barenholz Fund, which was established by the Hebrew University with royalties obtained from Y.B.’s inventions and is used to support research in the Barenholz Lab. The work of A.G.F. was funded by Xunta de Galicia (Grupo de referencia competitiva ED431C 2016041). We thank A. L. Chun of Science Story Lab for comments.

Author information


  1. Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary

    • Janos Szebeni
  2. SeroScience Ltd, Budapest, Hungary

    • Janos Szebeni
  3. Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary

    • Janos Szebeni
  4. Translational Bio-Nanosciences Laboratory, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA

    • Dmitri Simberg
  5. Immunology, Centro de Investigaciones Biomédicas (CINBIO), Centro de Investigación Singular de Galicia, Instituto de Investigación Sanitaria Galicia Sur (IIS-GS), University of Vigo, Vigo, Spain

    • África González-Fernández
  6. Department of Biochemistry, Institute for Medical Research Israel–Canada, Hebrew University–Hadassah Medical School, Jerusalem, Israel

    • Yechezkel Barenholz
  7. Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA

    • Marina A. Dobrovolskaia


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All authors wrote the paper.

Competing interests

J.S. is involved in SeroScience Ltd’s CRO activity providing immune toxicology services. J.S. and Y.B. are co-inventors on US patent 9,078,812B2, 14 July 2015, relevant to the use of liposomal carrier as desensitizing agent and co-owned by Semmelweis University, Hungary and Hebrew University, Israel. Y.B. is one of the inventors of two patents relevant to Doxil: US Patent 5,192,549, 9 March 1993, and US Patent 5,316,771, 31 May 1994. Both patents expired in March 2010. The Hebrew University received royalties from Doxil sales until the patent expiration. The Barenholz Fund, established with a portion of these royalties, is used to support research in Y.B.’s laboratory, including this study. The other authors declare no competing interests related to the subject described in the manuscript.

Corresponding author

Correspondence to Marina A. Dobrovolskaia.

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