- Expected to Accelerate the Introduction of Animal Replacement Tests in the Safety Assessment of Nanomaterials and Nanopharmaceuticals
The Korea Institute of Standards and Science (KRISS) has developed an organoid culture method that can accurately assess the toxicity of nanomaterials on the human body. It is expected to overcome the limitations of the existing culture method and accelerate the practical use of nanomaterials and nanopharmaceuticals.
Organoids are organelles produced by growing human stem cells in vitro. Although it is attracting attention as a next-generation toxicity assessment tool to replace animal testing due to its high human simulation, it has the disadvantage of being difficult to standardize due to the limitations of the culture method.
In the conventional organoid culture method, cells are embedded in extracellular matrix to form a three-dimensional structure, solidified into a dome, and then cultured by adding a culture medium. This method creates an imbalance in oxygen supply due to the difference in thickness between the center and the edge of the formed extracellular matrix dome, which makes it difficult to divide the organoids because they do not grow to a uniform size and aggregate like soap bubbles in the dome. The biggest problem is that nanomaterials cannot penetrate into the dome, making it impossible to accurately confirm the effect on the organoid.
The organoid culture method developed this time involves floating an organoid by mixing an extracellular matrix with the culture medium itself. It is suitable for practical use because organoids can be produced in a relatively uniform size and can be easily divided into equal numbers. In actual industrial sites, a high-speed mass screening technique is used that simultaneously tests the response to nanomaterials after dividing the cells into up to 1,000 containers, so uniform production and division are essential.
Another major advantage is that nanomaterials easily reach the organoids because, unlike conventional culture methods, there is no solidified extracellular matrix dome. It has the same level of nanomaterial permeability as the two-dimensional cell model currently used in industry. This is the first time in the world that a culture method has been developed to test the penetration of nanomaterials into an organoid.
The KRISS Nanobio Measurement Group tested the toxicity of nanomaterials by first culturing liver organoids for three days using the existing method to remove the extracellular matrix dome and then suspending them in a culture medium mixed with extracellular matrix at a concentration of 5%. The results of treating and comparing zinc oxide nanoparticles (ZnO NPs), a liver toxic substance, and non-toxic gold nanoparticles (AuNPs) showed that each substance is toxic, unlike the existing culture method.
Ahruem Baek, a senior researcher at KRISS, said, "Based on this achievement, we will contribute to the development of the domestic nanoindustry by establishing a standard evaluation method for nanomaterials and nanopharmaceuticals using organoids."
This achievement is expected to contribute to the safe use of nanomaterials in various strategic technologies such as food, pharmaceuticals, cosmetics, energy and semiconductors by enabling rapid and accurate safety evaluation of nanomaterials and nanopharmaceuticals using organoids.
Tae Geol Lee, head of the KRISS Nano Safety Technology Support Center, emphasized, "It is meaningful to develop the world's first organoid-based accurate safety evaluation technology for nanomaterials through convergence collaborative research with hospitals at a time when the need for animal replacement testing methods is increasing day by day at the Ministry of Food and Drug Safety and the U.S. FDA".
The research, conducted in collaboration with the University of Chiatrics, was supported by the Ministry of Science and ICT's Nano Safety Technology Support Center Project, the Science Challenges Challenge Convergence Research and Development Project, the Ministry of Trade, Industry and Energy's 3D Biological Organization Chip-based New Drug Development Platform, and the KRISS Basic Project. The achievements were published in January in Nano Letters (IF: 10.8), a prestigious academic journal in the field of nanotechnology.
