MiRNA-520a-3p combined with folic acid conjugated Fe2O3@PDA multifunctional nanoagents for MR imagine and antitumor gene-photothermal therapy

Nanotechnology. 2023 Jun 29;34(37). doi: 10.1088/1361-6528/acd5d9.

Abstract

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.

Keywords: Osteosarcoma; folic acid; gene therapy; magnetic resonance imaging; miR-520a-3p; photothermal therapy.

MeSH terms

  • Adolescent
  • Bone Neoplasms*
  • Cell Line, Tumor
  • Folic Acid
  • Humans
  • Magnetic Resonance Imaging
  • MicroRNAs* / genetics
  • Nanoparticles*
  • Osteosarcoma* / genetics
  • Osteosarcoma* / therapy
  • Photothermal Therapy

Substances

  • MicroRNAs
  • polydopamine
  • Folic Acid