Multifunctional nanoparticles as enhanced rheumatoid arthritis theranostic agent via sequential activated macrophages targeting and responsive dexamethasone release

Abstract Dexamethasone (DEX) is widely used in the treatment of rheumatoid arthritis (RA), however serious side effects will be generated after long-term use of it. In this study, a nanotheranostic agent (HCPC/DEX NPs) was designed to improve the therapeutic effect of RA. HCPC/DEX NPs can responsively release drug in the presence of H2O2 and acidic condition, and can prevent drug from excessively leaking in neutral environment. Under the action of hyaluronic acid, HCPC NPs can be selectively taken up by activated macrophages and then release drug in cells. After intravenous administration, HCPC/DEX NPs can be accumulated in adjuvant-induced arthritis (AA) rat joints, and showed better RA treatment effect compared with DEX. HCPC/DEX NPs can effectively alleviate paw swelling, repaire cartilage injury, and reduce inflammatory cell infiltration and proinflammatory cytokines secretion in AA rats. And HCPC/DEX NPs caused no side effects on main organs of normal rats. Our research indicated that HCPC/DEX NPs is an effective and safe RA theranostic agent and has potential application prospects in enhanced RA treatment.