Osteosarcoma (OS) is a primary malignant bone tumor that occurs mainly in adolescents. Researchers are devoting to develop combination therapy methods in a multifunctional nanoplatform for the treatment of osteosarcoma. The results of previous research have shown that up-regulation of miR-520a-3p could induce anticancer effects in osteosarcoma. In order to improve the effect of gene therapy (GT), we attempted to carry miR-520a-3p in a multifunctional vector for comprehensive therapy. Fe₂O₃is a type of magnetic resonance imaging (MRI) contrast that is widely used as a drug delivery agent. When coated with polydopamine (PDA), it can also be used as a photothermal therapy (PTT) agent (Fe₂O₃@ PDA). To deliver nanoagents targeted to a tumor site, folic acid (FA) conjugated with Fe₂O₃@PDA was manufactured as FA-Fe₂O₃@PDA. FA was chosen as the target molecule to enhance utilization and reduce toxicity of nanoparticles. However, the therapeutic efficacy of FA-Fe₂O₃-PDA combined with miR-520a-3p has not yet been studied. In this study, we synthesized FA-Fe₂O₃@PDA-miRNA and investigated the potential of combining PDA regulated PTT and miR-520a-3p regulated GT to kill osteosarcoma cells. The results indicated that down-regulation of interleukin 6 receptor (IL6R) by miR-520a-3p and the photothermal ability of PDA could induce satisfactory anticancer effects in osteosarcoma, and the curative ratio was better than that used alone PTT or GT. Moreover, as a kind ofT₂magnetic contrast, miRNA-Fe₂O₃@PDA-FA can be used for MRI. These findings indicated that miRNA-Fe₂O₃@PDA-FA is an effective anti-tumor nanovector for PTT combined with GT.

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