Sci. Adv. 2, e1601039 (2016)

The ability to integrate inorganic nanomaterials with biological systems presents exciting opportunities to design therapeutic and diagnostic devices that can be incorporated directly into cells. Silicon nanowires (SiNWs) are biocompatible, possess unique electronic properties and can host a range of functional groups on their surfaces, making them an ideal platform for such devices. They have already been exploited as biosensors and drug delivery agents, but little is known about how these materials enter cells or how they behave once inside. This is especially true for systems where the nanowires are not labelled with tracking markers that could potentially alter the nanowire-cell interactions.

Now, Zimmerman et al. report on a technique obtained by combining electron microscopy with optical imaging to visualize how endothelial cells — those lining the walls of blood vessels — internalize label-free SiNWs. They show that cell entry occurs via a phagocytosis pathway: the membrane extends to surround and engulf a nanowire and the resulting vesicle breaks off inside the cell. The process is morphology-dependent so the cell can distinguish between high-aspect ratio wires and particles of other shapes. Once internalized, cellular machinery shuttles the vesicle in short, rapid bursts from the edge of the cell to the area around the nucleus, where the nanowires eventually cluster inside larger lysosomal compartments. This fresh insight may prove invaluable when it comes to designing future devices. Moreover, whereas endothelial and macrophage cells spontaneously internalize SiNWs, neurons and cardiac muscle cells are found to reject them, implying that SiNW-based therapeutic devices could be made to target specific cell types.