Inflammation‐Targeting Mesenchymal Stem Cells Combined with Photothermal Treatment Attenuate Severe Joint Inflammation

Current clinical therapeutic efficacy for the treatment of osteo‐ and rheumatoid‐arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un‐modified or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation‐mediated education process is demonstrated. To reinforce the limited anti‐inflammatory activity of MSCs, gold nanostar loaded with triamcinolone is conjugated to MSC. Furthermore, near‐infrared laser‐assisted photothermal therapy (PTT) induced by gold nanostar significantly elevates the anti‐inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, is downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell is inhibited. Collectively, inflammation‐targeting MSCs conjugated with triamcinolone‐loaded gold nanostar (Edu‐MSCs‐AuS‐TA) promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu‐MSCs‐AuS‐TA significantly alleviate arthritis‐associated pain, improve general locomotor activity, and more importantly, induce cartilage regeneration even for severe stages of arthritis model. Gold nanostars‐conjugated mesenchymal stem cells, functionalized with triamcinolone, serve as a potent corticosteroids. Their therapeutic effectiveness is enhanced by near‐infrared laser irradiation, generating localized heat. Thermo‐responsive T lymphocytes exhibit diminished activity, attribute to interleukin 22 receptor inactivation under NIR laser exposure. This multifaceted approach adds therapeutic modulation in the treatment of severe arthritis.