Thiol-Functionalized, Antioxidant, and Osteogenic Mesoporous Silica Nanoparticles for Osteoporosis

Abstract

Osteoporosis is a chronic bone disorder characterized by decreased bone mass, leading to brittle bones and fractures. Oxidative stress has been identified as the most profound trigger for the initiation and progression of osteoporosis. Current treatment strategies do not induce new bone formation and fail to address a high level of reactive oxygen species (ROS). Mesoporous silica nanoparticles (MSNs) have been explored in bone tissue regeneration owing to their inherent osteogenic property, but they lack antioxidant and cell adhesion properties, required in such applications. We have developed thiolated, bioactive mesoporous silica nanoparticles (MSN-SH) to address this challenge. MSNs were fabricated using the Stöber method, and 11% of the surface was functionalized post-synthesis with thiol groups using MPTMS to obtain MSN-SH. The particle size measured by the dynamic light scattering technique was found to be around 300 nm. The surface morphology was investigated using HR-TEM, and their physical and chemical properties were characterized using various spectroscopic techniques. They exhibited more than 90% antioxidant activity, neutralized ROS formed in cells, and provided protection against ROS-induced cell damage. The cell viability assay in murine osteoblast precursor cells (MC3T3) showed that MSN-SH is cell-proliferative in nature with 140% cell viability. Osteogenic potential was evaluated by measuring the ALP activities, calcium deposition, and gene expression levels of osteogenic markers, such as RUNX2, ALP, OCN, and OPN, and results revealed that MSN-SH increases calcium deposition and induces osteogenesis through upregulation of osteogenic genes and markers without the involvement of any osteogenic supplements. Besides promoting osteogenesis, MSN-SH was found to inhibit osteoclastogenesis. The nanomaterial was found to be regenerative in nature, and it stimulated migration of osteoblast cells and caused a complete wound closure within 48 h. We were able to achieve a multifunctional nanomaterial by simply modifying the surface. MSNs have been explored for bone tissue engineering/osteoporosis as a composite system incorporating metals, like gold and cerium, or as a nanocarrier loaded with growth factors or active drugs. This study offers a simple and economical method to enhance the existing properties of MSNs and impart new activities by a single-step surface modification. It can be concluded that MSN-SH holds promise as a complementary and alternate treatment for osteoporosis along with the standardized therapy.

Keywords: antioxidant; bone mineralization; osteoporosis; silica nanoparticles; thiolation.