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Rheumatoid arthritis is a systemic inflammatory disease that can lead to articular cartilage destruction and periarticular bone erosion, thus ultimately compromising joint integrity and function. Anti-inflammatory drugs and biological agents are commonly used to treat rheumatoid arthritis, but they cannot selectively target inflamed joints, because of their systemic mechanisms, short half-lives and low bioavailability. Consequently, these agents must be used at high doses and delivered frequently, thereby increasing costs and the risk of adverse effects. Drug delivery systems, such as nanoparticles, liposomes and micelles, can significantly prolong drug half-life in the body and enable targeted delivery into the joints. In this review, we comprehensively describe the pathogenesis and clinical diagnosis of rheumatoid arthritis, and summarize recent advances in targeted therapeutic strategies, particularly nano-targeting systems for rheumatoid arthritis.

Cell surface thiols can be targeted by thiol-reactive groups of various materials such as peptides, nanoparticles, and polymers. Here, we used the maleimide group, which can rapidly and covalently conjugate with thiol groups, to prepare surface-modified liposomes (M-Lip) that prolong retention of doxorubicin (Dox) at tumor sites, enhancing its efficacy. Surface modification with the maleimide moiety had no effect on the drug loading efficiency or drug release properties. Compared to unmodified Lip/Dox, M-Lip/Dox was retained longer at the tumor site, it was taken up by 4T1 cells to a significantly greater extent, and exhibited stronger inhibitory effect against 4T1 cells. The in vivo imaging results showed that the retention time of M-Lip at the tumor was significantly longer than that of Lip. In addition, M-Lip/Dox also showed significantly higher anticancer efficacy and lower cardiotoxicity than Lip/Dox in mice bearing 4T1 tumor xenografts. Thus, the modification strategy with maleimide may be useful for achieving higher efficient liposome for tumor therapy.

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