Nanoceria provides antioxidant and osteogenic properties to mesoporous silica nanoparticles for osteoporosis treatment

Osteoporosis, a chronic metabolic bone disease, is the most common cause of fractures. Drugs for treating osteoporosis generally inhibit osteoclast (OC) activity, but are rarely aimed at encouraging new bone growth and often cause severe systemic side effects. Reactive oxygen species (ROS) are one of the key triggers of osteoporosis, by inducing osteoblast (OB) and osteocyte apoptosis and promoting osteoclastogenesis. Here we tested the capability of the ROS-scavenger nanoceria encapsulated within mesoporous silica nanoparticles (Ce@MSNs) to treat osteoporosis using a pre-osteoblast MC3T3-E1 cell monoculture in stressed and normal conditions. Ce@MSNs (diameter of 80 +/- 10 nm) were synthesised following a scalable two-step process involving sol-gel and wet impregnation methods. The Ce@MSNs at concentration of 100 mu g mL(-1) induced a significant reduction in oxidative stress produced by t-butyl hydroperoxide and did not alter cell viability significantly. Confocal microscopy showed that MSNs and Ce@MsNs were internalised into the cytoplasm of the pre-osteoblasts after 24 h but were not in the nucleus, avoiding any DNA and RNA modifications. Ce@MSNs provoked mineralisation of the pre-osteoablasts without osteogenic supplements, which did not occur when the cells were exposed to MSN without nanoceria. In a co-culture system of MC3T3-E1 and RAW264.7 macrophages, the Ce@MSNs exhibited antioxidant capability and stimulated cell proliferation and osteogenic responses without adding osteogenic supplements to the culture. The work brings forward an effective platform based for facile synthesis of Ce@MSNs to interact with both OBs and OCs for treatment of osteoporosis. Statement of significance Current therapies that treat osteoporosis only target osteoclasts (OCs), using drugs, leading to side effects. Here, new multicomponent 80 nm spherical nanoparticles (Ce@MSNs) combine antioxidant, osteogenic and anti-osteoclastogenic properties. Ce@MSNs interact with both osteoblast (OBs) and OCs in co-culture of osteoblasts and macrophages. Ce@MSNs stimulated osteoblast cells to produce bone matrix and demonstrated antioxidant properties in a co-culture cells without osteogenic supplements. Ce@MSNs have potential for treating osteoporosis and they could be adapted Ce@MSNs for the treatment of other diseases caused by oxidative stress. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

Ce@MSNs, as ROS-scavenger nanoceria, showed potential in treating osteoporosis by inducing mineralisation in pre-osteoblasts and exhibiting antioxidant capability without altering cell viability significantly. The nanoparticles also stimulated cell proliferation and osteogenic responses, indicating their potential for treating diseases caused by oxidative stress.