To test the effects of nanoparticle size on cell behavior spherical silica nanoparticles were synthesized at 50, 100, 200, and 450 nm (clockwise from top left).
To test the effects of nanoparticle size on cell behavior spherical silica nanoparticles were synthesized at 50, 100, 200, and 450 nm (clockwise from top left).

Cells interact with nanoscale materials and could offer a means to influence biological activity. Silica and similar materials like bioactive glass are particularly interesting for bone repair and dental applications because of their strength and biocompatibility. Now researchers have found that not only do bone cells ‘prefer’ one size of nanoparticle, they can tell the difference between one material and another.

The team from Emory University and the Atlanta Department of Veterans Affairs Medical Center led by George R. Beck Jr. took a systemic look at how bone-forming and -resorbing cells interact with nanoparticles of different size, surface charge, and composition [Ha et al., Acta Biomaterialia (2018),].

“We set out to assess some of the physical properties that influence [the] intrinsic biological activity of silica nanoparticles towards the two cell types responsible for bone homeostasis: bone-forming osteoblasts and bone-resorbing osteoclasts,” explains Beck. “To our knowledge this is one of the most comprehensive studies of the effects of physical properties of nanoparticles on modulating complex cell behavior.”

First the researchers compared how spherical silica nanoparticles of varying sizes from small (50 nm) to large (450 nm), prepared using the sol-gel method, interact with osteoblasts. Gold and polystyrene nanoparticles were then compared with the best-performing silica particles.

“We found that the positive effect of nanoparticles on osteoblasts is strongly influenced by size and silica produces the greatest enhancement of osteoblast differentiation,” explains Beck.

The smallest nanoparticles show the most significant and consistent enhancement of osteoblast differentiation and mineralization. The largest particles, by contrast, appear to have a negative effect on mineralization. When it comes to osteoclasts, the picture is different, the team found. With this type of cell, nanoparticle size has little influence while negative surface charge strongly inhibits their behavior.

“The optimal nanoparticle for enhancement of osteoblastogenesis is a spherical silica particle of 50 nm, whereas most nanoparticles can inhibit osteoclastogenesis provided they are relatively negatively charged,” points out Beck.

Exactly how osteoblasts and osteoclasts recognize and respond to different nanoparticle is likely to be down to the presence of surface proteins that bind to the particles, creating what is known as a ‘protein corona’.

“The most challenging outcome to explain is the fact that osteoblasts appear to ‘recognize’ silica nanoparticles in deference to either gold or polystyrene although the particles are the same size and spherical,” says Beck.

The findings indicate that silica nanoparticles could be used as a dual agent to simultaneously stimulate bone-forming osteoblasts and inhibit bone-resorbing osteoclasts. More broadly, the work opens the door for nanosystems designed to target specific cell types with enhanced therapeutic effects.