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The effects of contamination during nanoparticle production
(Nanowerk Spotlight) A new study by Swedish researchers shows that gold nanospheres with a diameter of 7 nm, produced in a conventional laboratory surrounding, activate human antigen presenting dendritic cells (DCs) to induce proliferation of peripheral blood mononuclear cells (PBMC), mixed with either allergenic or autologous DCs. This effect was found to be due to endotoxin (lipopolysaccharide, LPS) contamination of the nanoparticles. When particles were produced in a controlled way eliminating endotoxin contamination, the activation of the DCs did not take place.
Dr. Susanne Gabrielsson from the Clinical Allergy Research Unit at the Karolinska Institute in Stockholm, explained these findings to Nanowerk: "Pure gold nanoparticles do not affect the "sentinels of the immune system" – DCs. Thus, our results support the suitability of gold nanoparticles as inert carriers for use in biomedical applications. Our findings also emphasize the importance of combining knowledge within materials science with that of biomedicine when generating new advanced materials, to avoid misinterpretation of results."
"At present, nanoscience focuses mainly on the search for new materials and techniques, and safety and biomolecular aspects are often postponed for future studies" says Gabrielsson. " Contaminants, such as LPS, as found in our study, may lead to erroneous conclusions that cause developers to abandon what might be a promising material. If LPS or other adjuvants are to be used, they need to be applied in a controlled manner."
In a new paper, titled "The Importance of an Endotoxin-Free Environment during the Production of Nanoparticles Used in Medical Applications" Gabrielsson, together with first author Helen Vallhov and colleagues from Stockholm University and the Royal Institute of Technology, explain the problem of LPS contamination of nano particles and describe ways to reduce contamination.
The scientists point out that particles produced in a semi-clean environment affect phenotype and function of DCs. Since DCs are highly present in the lungs, inhalation of contaminated particles may potentially lead to unwanted immune modulation. Therefore, to minimize the risks, the contamination of nanomaterial used also in non-biomedical applications should be avoided.
LPS contamination is likely avoided in a GLP (good laboratory practice) laboratory when particles are produced for biomedical applications. "However" says Gabrielsson, "LPS levels should always be analyzed in nanoparticle preparations if they are to be tested on living cells or animals. Furthermore, LPS contamination should be avoided in nanoparticles used for other applications, since there is a risk of unwanted immune modulation if particles enter the body e.g. through inhalation."
However, LPS also may have advantageous synergetic effects, depending on the desired cellular/medical effects, and immune modulating particles might be desirable in specific applications such as vaccine delivery. Further research will be directed towards understanding, and eventually controlling, how LPS or other agents, combined with specific antigens and added on the surface of nanoparticles, may direct the immune response in a specific way.
Michael Berger By – Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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