(a) Confocal image of Ce@MSNs uptaken into MC3T3-E1 cells. (b) and (c) Transmission electron microscope images of 80 nm MSNs containing 3 nm nanoceria.
(a) Confocal image of Ce@MSNs uptaken into MC3T3-E1 cells. (b) and (c) Transmission electron microscope images of 80 nm MSNs containing 3 nm nanoceria.

Osteoporosis, which causes loss of bone density, affects over 22 million women and 5 million men globally, costing tens of billions annually in direct and indirect health costs. With growing aged populations, these numbers are expected to rise dramatically in coming decades.

The condition arises when the processes of bone formation and break down become unbalanced. One of the triggers is reactive oxygen species (ROS), which induce programmed cell death (or apoptosis) of bone-forming cells (osteoblasts) and mature bone cells (osteocytes) while boosting the formation of osteoclasts that break down and resorb bone. Increased osteoclast activity when bone cells are stressed leads to decreased bone mass and mineral density, increasing the likelihood of fractures. Existing drug treatments tend to focus on suppressing this activity but can cause serious side effects. Now researchers from Imperial College London and King Mongkut’s University of Technology have come up with a new approach that scavenges ROS and boosts new bone formation [Pinna et al., Acta Biomaterialia 122 (2021) 365-376, https://doi.org/10.1016/j.actbio.2020.12.029 ].

The approach relies on porous silica nanoparticles impregnated with the rare-earth metal oxide, ceria. Silica boosts bone-forming activity by releasing metal ions such as calcium and strontium. Ceria, meanwhile, possesses a unique chemistry allowing it to act as a radicals and reactive oxygen species sink. The researchers synthesized tiny (3 nm) nanoceria particles encapsulated within mesoporous silica nanoparticles (Ce@MSNs) using a two-step process involving sol-gel and wet impregnation methods. The MSNs act as a sponge, absorbing cerium precursor species that, at high temperature, form nanoceria in situ.

“The silica can be thought of as the high porosity delivery vehicle for the nanoceria, which acts as an antioxidant,” explain first author Alessandra Pinna and Julian R. Jones, who led the effort.

During in vitro tests, 80-nm diameter Ce@MSNs reduced oxidative stress and increased bone formation without affecting cell viability. The nanoparticles are absorbed into the cytoplasm of pre-osteoblasts, encouraging mineralization and stimulating cell proliferation without the need for osteogenic supplements.

“[The nanoparticles] have dual osteogenic and antioxidant properties,” say Pinna and Jones. “The release of soluble silica from MSNs stimulates osteoblast differentiation and the production of new bone matrix. When ceria is nano-sized the surface area dramatically increases, allowing greater oxygen exchange so it acts as an antioxidant by scavenging free radicals,” they explain.

The dual-material nanoparticles, with their synergistic properties, could be formulated as a capsule for oral delivery or injected into the affected site directly to treat osteoporosis. The researchers believe the approach could be adapted to treat other conditions caused by oxidative stress such as cancer and brain disease. The challenge now is to demonstrate the safety of the nanoparticles for human use, says Jones.