Pericellular matrix enhances retention and cellular uptake of nanoparticles

A hydrated gel-like pericellular matrix (PCM) covers the surface of all eukaryotic cells and plays a key role in many cellular events, but its effect on nanoparticle internalization has not been studied. Here, using cells with various PCM thicknesses and gold nanoparticles as probes, we demonstrate that, rather than being a barrier to all foreign objects, the PCM can entrap and accumulate NPs, restrict and slow down their diffusion, and enhance their cellular uptake efficiency. Moreover, this newly discovered PCM function consumes energy and seems to be an integral part of the receptor-mediated endocytosis process. These findings are important in understanding the delivery mechanisms of nanocarriers for biomedical applications.