Multimodal nanoparticles (gold in polylactide) and their effect on three-dimensional cell cultures as organ models

• Applicants: Professor Dr. Matthias Epple; Professorin Dr. Astrid M. Westendorf
• Subject Area: Biological and Biomimetic Chemistry ; Biomaterials
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 417844584

• Final Report Year: 2023

Final Report Abstract

Very small gold nanoparticles can easily penetrate the membranes of intestinal epithelial cells and colorectal cancer cells. This was shown for in three-dimensional cell murine spheroids (400 µm) and also in primary organoids directly generated from the human gut biopsies. In contrast, dissolved dyes were not taken up by any of these cells or three-dimensional structures. The distribution of fluorescent ultrasmall gold nanoparticles inside cells, spheroids, and gut organoids was examined by optical imaging. Nanoparticles conjugated with a cytostatic drug exhibited a significantly stronger cytotoxicity than the dissolved drug alone, probably because the nanoparticles entered the interior of a spheroid much more easily than the dissolved drug. This makes such nanoparticles promising for application in cancer therapy. The uptake of these nanoparticles by bacteria occurred within 1 to 3 hours as shown by optical microscopy, including super-resolution microscopy. Importantly, the nanoparticles showed no toxicity to the bacteria, indicating a non-lethal nature of the uptake, i.e. not related to cell injury. Thus, fluorescently labelled ultrasmall gold nanoparticles are promising tools to study the uptake of particles from the environment by bacteria (without causing lethal effects), possibly for a future application as antimicrobial agent that acts from within a bacterium. This could be a path to combat the ever-increasing bacterial resistance to antibiotics.

Publications

• Bacteria (E. coli) take up ultrasmall gold nanoparticles (2nm) as shown by different optical microscopic techniques (CLSM, SIM, STORM). Nano Select, 3(10), 1407-1420.
  Białas, Nataniel; Sokolova, Viktoriya; van der Meer, Selina Beatrice; Knuschke, Torben; Ruks, Tatjana; Klein, Kai; Westendorf, Astrid M. & Epple, Matthias
  
• Jahrestagung der Deutschen Gesellschaft für Biomaterialien e.V. (DGBM), Essen, 15.- 17.09.2022, "The application of optical high-resolution microscopy (CLSM, SIM, STORM) to study the interaction between ultrasmall gold nanoparticles and bacteria"
  N. Bialas; V. Sokolova; T. Ruks; K. Klein; T. Knuschke; A.M. Westendorf; M. Epple & Jakobs, L.
  
• Uptake of Functional Ultrasmall Gold Nanoparticles in 3D Gut Cell Models. Small, 18(31).
  Sokolova, Viktoriya; Ebel, Jana‐Fabienne; Kollenda, Sebastian; Klein, Kai; Kruse, Benedikt; Veltkamp, Claudia; Lange, Christian M.; Westendorf, Astrid M. & Epple, Matthias