In Situ Visualization of Dynamic Cellular Effects of Phospholipid Nanoparticles via High-Speed Scanning Ion Conductance Microscopy.

Phospholipid nanoparticles have been actively employed for numerous biomedical applications. A key factor in ensuring effective and safe applications of these nanomaterials is the regulation of their interactions with target cells, which is significantly dependent on an in-depth understanding of the nanoparticle-cell interactions. To date, most studies investigating these nano-bio interactions have been performed under static conditions and may lack crucial real-time information. It is, however, noteworthy that the nanoparticle-cell interactions are highly dynamic. Consequently, to gain a deeper insight into the cellular effects of phospholipid nanoparticles, real-time observation of cellular dynamics after nanoparticle introduction is necessary. Herein, a proof-of-concept in situ visualization of the dynamic cellular effects of sub-100 nm phospholipid nanoparticles using high-speed scanning ion conductance microscopy (HS-SICM) is reported. It is revealed that upon introduction into the cellular environment, within a short timescale of hundreds of seconds, phospholipid nanoparticles can selectively modulate the edge motility and surface roughness of healthy fibroblast and cancerous epithelial cells. Furthermore, the dynamic deformation profiles of these cells can be selectively altered in the presence of phospholipid nanoparticles. This work is anticipated to further shed light on the real-time nanoparticle-cell interactions for improved formulation of phospholipid nanoparticles for numerous bioapplications.