Multi-cell, non-invasive, online monitoring of PLA-coated magnetic nanoparticles uptake by MCF-7 cells using digital holographic microscopy

The application of nanoparticles (NPs) in medicine as delivery platforms has experienced a significant expansion in the past decade and as a result, various imaging techniques have been applied to monitor cellular NP uptake. Although, high-resolution images of a NP contained within the cell can be generated allowing for quantification, live NP monitoring remains a challenge. Digital holographic microscopy (DHM) has emerged a convenient label-free method to study the cell surface dynamics in real-time by recording a hologram of an interference pattern generated by light which has been scattered from the cell sample, compared to the reference sample. Herein, we report that DHM can be used to monitor the cellular NP uptake in real-time by analysing the changing in surface roughness. As a proof-of-concept, we demonstrated an increase in cell roughness of MCF-7 human breat cancer cells when PLA-coated magnetite, Fe 3 O 4 NPs interacted with the MCF-7 cell surface. By measuring cell roughness every minute, the entire NP internalisation process could be monitored. DHM also addressed challenges within existing imaging techniques, by enabling multi-cellular analysis as well as successfully monitor how changes in NP density and size impacted internalisation rate, highlighting how this method can be further applied in monitoring cellular dynamics and in the development of future nanoparticle-based therapeutics, as well as, tissue engineering. • Uptake of magnetic nanoparticles (NPs) by MCF-7 breast cancer cells was monitored by Digital holographic microscopy (DHM). • The NP uptake process was monitored based on the change of roughness on the cell surface induced by loading NPs. • The effect of the density of NPs on uptake was small, while the particle size showed a more significant effect. • Roughness kurtosis mode was more sensitive for uptake monitoring than roughness skewness. • The technique was not size-limited as smaller NPs (30 nm in diameter) have shown a faster uptake.