A novel Anti-ROS osteoblast-specific delivery system for ankylosing spondylitis treatment via suppression of both inflammation and pathological new bone formation

• Published in: Journal of nanobiotechnology 2023-05, Vol.21 (1), p.168-168, Article 168
• Main Authors: Zheng, Guan, Peng, Xiaoshuai, Zhang, Yunhui, Wang, Peng, Xie, Zhongyu, Li, Jinteng, Liu, Wenjie, Ye, Guiwen, Lin, Yucong, Li, Guojian, Liu, Huatao, Zeng, Chenying, Li, Lihua, Wu, Yanfeng, Shen, Huiyong
• Format: Article
• Language: English
• Subjects: Animals; Ankylosing spondylitis; Anti-inflammatory agents; Aptamers; Arthritis; Bone growth; Bones; Care and treatment; Decomposition; Differentiation (biology); Disease; Drug delivery systems; Drugs; Growth; Health aspects; Inflammation; Inflammation - drug therapy; Inflammation - pathology; Joint diseases; Management; Manganese; Methods; Mice; MnFe2O4 nanoparticles; Nanomaterials; Nanomedicine; Nanoparticles; Nonsteroidal anti-inflammatory drugs; Ossification (ectopic); Ossification, Heterotopic - pathology; Osteoblasts; Osteogenesis; Pathogenesis; Reactive oxygen species; Rheumatic diseases; RNA, Small Interfering - pharmacology; ROS scavenging; Side effects; siRNA; Spectrum analysis; Spondylitis, Ankylosing - drug therapy; Spondylitis, Ankylosing - pathology; Targeted therapy; TNF inhibitors; Vehicles
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-01906-2

Ankylosing spondylitis (AS) is a common rheumatic disorder distinguished by chronic inflammation and heterotopic ossification at local entheses sites. Currently available medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) and TNF inhibitors, are limited by side effects, high costs and unclear inhibitory effects on heterotopic ossification. Herein, we developed manganese ferrite nanoparticles modified by the aptamer CH6 (CH6-MF NPs) that can efficiently scavenge ROS and actively deliver siRNA into hMSCs and osteoblasts in vivo for effective AS treatment. CH6-MF NPs loaded with BMP2 siRNA (CH6-MF-Si NPs) effectively suppressed abnormal osteogenic differentiation under inflammatory conditions in vitro. During their circulation and passive accumulation in inflamed joints in the Zap70 mouse model, CH6-MF-Si NPs attenuated local inflammation and rescued heterotopic ossification in the entheses. Thus, CH6-MF NPs may be an effective inflammation reliever and osteoblast-specific delivery system, and CH6-MF-Si NPs have potential for the dual treatment of chronic inflammation and heterotopic ossification in AS.