In Depth Mapping of Mesoporous Silica Nanoparticles in Malignant Glioma Cells Using Scattering-Type Scanning Near-Field Optical Microscopy.

Mesoporous silica nanoparticles (MSNPs) are promising nanomedicine vehicles due to their biocompatibility and ability to carry large cargoes. It is critical in nanomedicine development to be able to map their uptake in cells, including distinguishing surface associated MSNPs from those that are embedded or internalized into cells. Conventional nanoscale imaging techniques, such as electron and fluorescence microscopies, however, generally require the use of stains and labels to image both the biological material and the nanomedicines, which can interfere with the biological processes at play. We demonstrate an alternative imaging technique for investigating the interactions between cells and nanostructures, scattering-type scanning near-field optical microscopy (s-SNOM). s-SNOM combines the chemical sensitivity of infrared spectroscopy with the nanoscale spatial resolving power of scanning probe microscopy. We use the technique to chemically map the uptake of MSNPs in whole human glioblastoma cells and show that the simultaneously acquired topographical information can provide the embedding status of the MSNPs. We focus our imaging efforts on the lamellipodia and filopodia structures at the peripheries of the cells due to their significance in cancer invasiveness.