The synergy of photothermal therapy (PTT) and chemotherapy is widely regarded as an effective treatment for complex diseases, such as cancer and inflammation. In this paper, we report the synthesis of a nanoscaled drug delivery system, which was composed of a gold nanorod (GNR) as the photothermal agent and a mesoporous silica shell as the methotrexate (MTX) reservoir, named FAGMs. Due to folate modification on the surface, FAGMs targeted specifically activated macrophages in rheumatoid arthritis (RA). Under 808 nm laser irradiation, FAGMs could kill macrophages by reaching sufficient local hyperthermia with excellent efficiency in the photothermal conversion of GNRs. Meanwhile, internal heating caused hydrogen bond fracture; thus, MTX released rapidly from FAGMs for localized synergistic PTT and chemotherapy. The FAGMs had a mean particle size of about 180 nm and a zeta potential of 14.36 mV. The release rate of MTX from FAGMs in vitro increased markedly under 808 nm laser irradiation. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages when treated with FAGMs, suggesting that folic acid molecules enabled the enhancement of endocytosis into activated macrophages. In rats with adjuvant-induced arthritis, synergistic treatment excellently inhibited the progression of RA. These results demonstrated that FAGMs could be promising for the treatment of RA.
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