MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis

• Published in: Journal of nanobiotechnology 2020-08, Vol.18 (1), p.117-14, Article 117
• Main Authors: Lan, Qiumei, Lu, Rongbin, Chen, Haimin, Pang, Yunfen, Xiong, Feng, Shen, Chong, Qin, Zainen, Zheng, Li, Xu, Guojie, Zhao, Jinmin
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; Antiarthritic agents; Arthritis; Benzofurans; Biocompatibility; Biodynamics; Biomedical materials; Cartilage; Cartilage diseases; Cartilage targeting; Cells, Cultured; Chondrocytes - metabolism; Cognitive enhancement; Collagenase 3; Coumarins; Cytotoxicity; Diagnosis; Disease; Drug delivery; Drug delivery systems; Drugs; Enzymes; Gene expression; Health aspects; Herbal medicine; Hydrogen-Ion Concentration; Inflammation; Matrix metalloproteinase; Matrix Metalloproteinase 13 - metabolism; Matrix metalloproteinases; Mice; Mice, Inbred C57BL; Micelles; MMP-13/pH sensitive; Osteoarthritis; Osteoarthritis - metabolism; Peptides; pH effects; Theranostic Nanomedicine - methods; Theranostics; Traditional Chinese medicine; Vehicles
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-020-00666-7

Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA), which enables the development of stimulus-responsive drug delivery system with high specificity for OA. We herein demonstrate a nano-micelle based stimuli-responsive theranostic strategy with reporting and drug release controlled by acidic pH and MMP-13 for OA therapy. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro and vivo evidences.