期刊
BIOMATERIALS
卷 276, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121063
关键词
Rheumatoid arthritis; Sonodynamic therapy; Concave-cubic rhodium nanozyme; Sonosensitizer; Mutual-reinforcing
资金
- National Natural Science Foundation of China [81701817, 31971106, 81372124]
- National Key Research and Development Program of China [2020YFC1512304, 2020YFC1512301]
- Young Elite Scientists Sponsorship Program by Tianjin [0701320001]
- Major Special Projects of Tianjin [0402080005]
The strategy developed provides effective sonodynamic therapy under hypoxic microenvironment for the treatment of rheumatoid arthritis (RA), with promising prospects for highly efficient treatment.
Rheumatoid arthritis (RA) is an autoimmune disease associated with synovitis and cartilage destruction. Ultrasound (US)-driven sonodynamic therapy (SDT) possess a good application prospect in RA therapy because of its non-invasiveness and strong tissue penetration capabilities, which can kill activated synovial inflammatory cells. Nevertheless, the tiny accumulation of sonosensitizers in the joints and the hypoxic synovial microenvironment severely limit the therapeutic effect of SDT. Hence, we developed a sonosensitizer spafloxacin (SPX) doped and human serum albumin (HSA) loaded concave-cubic rhodium (Rh) nanozyme (Rh/SPX-HSA) to realize mutual-reinforcing SDT during ultrasonic activation. On the one hand, SPX would cause mitochondrial dysfunction by inducing excessive reactive oxygen species (ROS) production, thus suppressing fibroblast-like synoviocyte (FLS) under US conditions. On the other hand, concave-cubic rhodium was utilized as a nanozyme with endogenous peroxidase (POD) and catalase (CAT)-like enzyme activities, which not only relieved the hypoxia of the joint to resist angiogenesis, but also enormously ascended the SDT efficacy by rising 1O2 levels. Interestingly, the activity of nanozymes was also improved by the ultrasonic cavitation effect, thereby realizing mutual-reinforcing SDT. Overall, our strategy provided Rh-based to achieve effective SDT under hypoxic microenvironment, which offered a promising prospect for highly efficient treatment of RA.
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