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miRNA-520a-3p 联合叶酸修饰的 FeO@PDA 多功能纳米制剂用于磁共振成像和抗肿瘤基因-光热治疗。

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

机构信息

School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022, People's Republic of China.

Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130021, Jilin, People's Republic of China.

出版信息

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

DOI:10.1088/1361-6528/acd5d9
PMID:37192608
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. FeOis 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 (FeO@ PDA). To deliver nanoagents targeted to a tumor site, folic acid (FA) conjugated with FeO@PDA was manufactured as FA-FeO@PDA. FA was chosen as the target molecule to enhance utilization and reduce toxicity of nanoparticles. However, the therapeutic efficacy of FA-FeO-PDA combined with miR-520a-3p has not yet been studied. In this study, we synthesized FA-FeO@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 ofmagnetic contrast, miRNA-FeO@PDA-FA can be used for MRI. These findings indicated that miRNA-FeO@PDA-FA is an effective anti-tumor nanovector for PTT combined with GT.

摘要

骨肉瘤(OS)是一种主要发生在青少年中的原发性恶性骨肿瘤。研究人员致力于开发多功能纳米平台的联合治疗方法,用于治疗骨肉瘤。先前的研究结果表明,miR-520a-3p 的上调可以诱导骨肉瘤的抗癌作用。为了提高基因治疗(GT)的效果,我们试图在多功能载体中携带 miR-520a-3p 进行综合治疗。FeO 是一种广泛用作药物递送剂的磁共振成像(MRI)造影剂。当用聚多巴胺(PDA)涂覆时,它也可以用作光热治疗(PTT)剂(FeO@PDA)。为了将靶向肿瘤部位的纳米剂递送至肿瘤部位,制造了与 FeO@PDA 缀合的叶酸(FA)作为 FA-FeO@PDA。选择 FA 作为靶分子,以提高纳米粒子的利用率并降低其毒性。然而,FA-FeO-PDA 与 miR-520a-3p 联合的治疗效果尚未得到研究。在这项研究中,我们合成了 FA-FeO@PDA-miRNA,并研究了 PDA 调节的 PTT 和 miR-520a-3p 调节的 GT 联合杀死骨肉瘤细胞的潜力。结果表明,miR-520a-3p 下调白细胞介素 6 受体(IL6R)和 PDA 的光热能力可在骨肉瘤中诱导令人满意的抗癌作用,其治愈率优于单独使用 PTT 或 GT。此外,作为一种磁性对比剂,miRNA-FeO@PDA-FA 可用于 MRI。这些发现表明,miRNA-FeO@PDA-FA 是一种用于 PTT 联合 GT 的有效抗肿瘤纳米载体。

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