ROS-reactive PMS/PC drug delivery system improves new bone formation under diabetic conditions by promoting angiogenesis-osteogenesis coupling via down-regulating NOX2-ROS signalling axis

Wu，Zimei1; Hou，Qiaodan1; Chen，Tingting1; Jiang，Xingzhu1; Wang，Lulu1; Xu，Jing3; Wang，Lin1,2

2022-12-01

10.1016/j.biomaterials.2022.121900

BIOMATERIALS   Impact Factor & Quartile

0142-9612

1878-5905

Reactive oxygen species (ROS) overproduction and oxidative stress increases bone fragility and fracture risk in long-standing diabetes mellitus cases. In this study, a ROS-reactive drug delivery system was prepared to solve this issue by phenyl sulfide mesoporous silica nanoparticles (PMS) loaded with proanthocyanidin (PC). The effect of PMS/PC on new bone formation under diabetic conditions and the underlying mechanism was investigated in-vitro and in-vivo. The results illustrated that the PC was released from the ROS-reactive PMS/PC triggered by peripheral ROS and then eliminated excessive ROS, which achieved dynamic ROS regulation and reached ROS homeostasis finally. Furthermore, we found PMS/PC promoted osteoblastic differentiation in vitro and increased ossification in vivo by promoting the angiogenesis-osteogenesis coupling via down-regulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) to suppress ROS overproduction, preventing vascular oxidative stress. Therefore, our work has proved a therapeutic potential of ROS-reactive PMS/PC in the treatment of diabetic bone disease and indicates excellent prospects of PMS/PC to depress oxidative stress triggered by excessive ROS which is a key pathological factor in many systematic diseases.

Angiogenesis-osteogenesis coupling Diabetic bone disease Mesoporous silica nanoparticles NOX2-ROS signalling axis Proanthocyanidins

EI ; SCI

English

First ; Corresponding

Basic and Applied Basic Research Foundation of Guangdong Province[2022A1515012373];National Natural Science Foundation of China[81972045];

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000893574300001

ELSEVIER SCI LTD

20224613116467

Diseases ; Flavonoids ; Oxidative stress ; Silica nanoparticles ; Sulfur compounds ; Targeted drug delivery

Biology:461.9 ; Nanotechnology:761 ; Organic Compounds:804.1

MATERIALS SCIENCE

2-s2.0-85141766419

Scopus

1.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
2.Southern University of Science and Technology Hospital,Shenzhen,518055,China
3.Medical Research Center,Southern University of Science and Technology Hospital,Shenzhen,518055,China

Wu，Zimei,Hou，Qiaodan,Chen，Tingting,et al. ROS-reactive PMS/PC drug delivery system improves new bone formation under diabetic conditions by promoting angiogenesis-osteogenesis coupling via down-regulating NOX2-ROS signalling axis[J]. BIOMATERIALS,2022,291.

Wu，Zimei.,Hou，Qiaodan.,Chen，Tingting.,Jiang，Xingzhu.,Wang，Lulu.,...&Wang，Lin.(2022).ROS-reactive PMS/PC drug delivery system improves new bone formation under diabetic conditions by promoting angiogenesis-osteogenesis coupling via down-regulating NOX2-ROS signalling axis.BIOMATERIALS,291.

Wu，Zimei,et al."ROS-reactive PMS/PC drug delivery system improves new bone formation under diabetic conditions by promoting angiogenesis-osteogenesis coupling via down-regulating NOX2-ROS signalling axis".BIOMATERIALS 291(2022).