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K-State Today

December 14, 2017

Kansas State University contributes to understanding of nanomaterial immunosafety in medicine

By Zhenzhen Shi

A research team that includes scientists and modelers with Kansas State University's Institute of Computational Comparative Medicine, or ICCM, and Nanotechnology Innovation Center of Kansas State, or NICKS, has studied the inflammatory responses triggered by nanoparticles.

The study, "Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold nanoparticles, interferes with biocorona formation and induces human monocyte inflammatory activation," was recently published in Nanotoxicology, a top-ranked journal in the field of toxicology and medicine.

The advent of nanotechnology has attracted researchers' interests in many fields such as biomedical sciences and engineering, recognizing nanoparticles coated with organic molecules as one of the promising methods of drug delivery to targeted tissues — e.g., cancer cells — in humans.

"However, lipopolysaccharide, or LPS, or other substances in biological fluids or our environment may bind to nanoparticles and change the biological properties of nanoparticles," said Yang Li, former postdoc at NICKS and the first and corresponding author of this study. "We should be careful about biomedical application of nanoparticles because the contaminants in nanoparticles we are not aware of may induce unexpected toxicity. Therefore, we designed experimental studies to investigate if binding of such ubiquitous contaminant in environment may change physicochemical status of nanoparticles and induce further immune responses."

Other than the experimental studies, computational modeling also was developed to study a dose- and time-dependent binding capacity of LPS to the surface of nanoparticles.

"Computational simulation is a powerful tool for studying mechanisms underlying the interaction between various cellular components" said Zhenzhen Shi, a postdoc at the ICCM and the second author of this study. "We employed the modeling approach to simulate and estimate real-time binding process between LPS and nanoparticles."

By incorporating experimental data into the simulation study, Shi worked together with Majid Jaberi-Douraki from the math department to find the mathematical relationship between surface plasmon resonance and amount of LPS bound on the surface of nanoparticles.

Findings from this study suggested that distinguishing intrinsic nanoparticle biological effects caused by biologically active contaminants such as endotoxin or LPS is extremely important for an accurate interpretation of nano-bio interaction and nanosafety studies.

The research was collaborated internationally in six institutes, and led by researchers with the Italian National Research Council and Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. The project received funding from European Community's Seventh Framework Programme and National Natural Science Foundation of China. The experimental and modeling work of the study was partially supported by the ICCM and NICKS centers from the Kansas Bioscience Authority.

Collaborative researchers on this study included Isabella Radauer-Preiml, Ancuela Andosch, Ursula Lütz-Meindl, Jutta Horejs-Hoeck, Martin Himly and Albert Duschl, all with the University of Salzburg; Zhoumeng Lin and Majid Jaberi-Douraki, all with the Institute of Computational Comparative Medicine at Kansas State University; Nancy Monteiro-Riviere, with the Nanotechnology Innovation Center of Kansas State at Kansas State University; Eudald Casals, Macarena Cobaleda, and Victor Puntes, all with the Institut Català de Nanotecnologia; and Paola Italiani and Diana Boraschi, both with the Italian National Research Council.