Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis

Abstract

Guoying Deng1,*, Chenyun Dai2,*, Jinyuan Chen1, Anqi Ji1, Jingpeng Zhao1, Yue Zhai1, Yingjie Kang3, Xijian Liu4, Yin Wang5, Qiugen Wang1 1Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 2Institute of Translation Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 3Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 4College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China; 5Ultrasound Department of Shanghai Pulmonary Hospital, Tongji University, Shanghai, China *These authors contributed equally to this work Background: Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. Methods: The potential interferences Se@SiO2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. Results: In the present study, we found that in the rat model of ARDS, Se@SiO2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO2 could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Conclusion: Se@SiO2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy. Keywords: porous Se@SiO2 nanocomposites, methylprednisolone, osteonecrosis of femoral head, ROS damage, ARDS

Keywords

• Porous Se@SiO2 nanocomposites
• Methylprednisolone
• Osteonecrosis of femoral head
• ROS damage
• ARDS