The interaction of inert nano-particles with cells has significant effect on the potential cytotoxicity of the particles. The role of particle aspect ratio in the interaction with cells was largely studied in the literature; however non consistent conclusions were obtained. In the present study a detailed physical model is presented as well as a set of experimental work and a scan of literature data. The aim was to investigate the role of particle size and aspect ratio in cell uptake, and to examine possible sources of the literature inconsistency. Cells which provide the first line of contact with particles in the human body were incubated with seven types of particles. These included spherical and rod gold nanoparticles, as well as larger spherical polystyrene particles in various sizes. We stress that in order to achieve comparative insight careful attention needs to be given to the experimental conditions and to the data analysis. Furthermore, our physical model shows that conclusions regarding the role of aspect ratio in NP uptake largely depend on the radius of the particles. The aspect ratio cannot be regarded as a sole geometrical parameter which determines the interaction of inert nano-particles with cells. When discussing particles larger than 10 nm (for which passive diffusion is irrelevant), the effect of the aspect ratio flips depending on the particle thickness. For particles thicker than ∼35 nm, the longer they are the more toxic they would be, however this trend opposes for thinner NPs, where larger aspect ratio results in reduced uptake and toxicity. Therefore, rod non-functionalized particles whose thickness is between 15 and 30 nm, and are relatively long, are expected to be the safest, with minimal cytotoxicity.
Bibliographical noteFunding Information:
We are grateful to Natalie Orehov for the spinning disc microscopy images and Talya Millo for a fluorescence microscopy image. We would like to thank Dr Einat Zelinger, director of the CSI microscopy core facility at HUJI agriculture campus, for the confocal imaging of HaCat cells. We would like to thank Dr Yael Levi-Kalisman from the HUJI Center for Nanoscience and Nanotechnology for the Cryo TEM images of the gold nanoparticles. This project was funded by the Israeli Ministry of Science and Technology, grant #3-13574, European Research Council (ERC)-PoC 101061967, ERC-starter grant 756762, Israel Science Foundation grant no. ISF 877/19 and the Teacher-Scholars program of The Hebrew University of Jerusalem supported by the Jerusalem Municipality, JDA and the Trump Foundation.
© 2022 The Author(s).