Precision Health Program, Michigan State University.
Precision Health Program, Michigan State University; Department of Radiology, College of Human Medicine, Michigan State University.
J Vis Exp. 2024 Aug 23(210). doi: 10.3791/66961.
Metastatic breast cancer is a devastating disease with very limited therapeutic options, calling for new therapeutic strategies. Oncogenic miRNAs have been shown to be associated with the metastatic potential of breast cancer and are implicated in tumor cell migration, invasion, and viability. However, it can be difficult to deliver an inhibitory RNA molecule to the tissue of interest. To overcome this challenge and deliver active antisense oligonucleotides to tumors, we utilized magnetic iron oxide nanoparticles as a delivery platform. These nanoparticles target tissues with increased vascular permeability, such as sites of inflammation or cancer. Delivery of these nanoparticles can be monitored in vivo by magnetic resonance imaging (MRI) due to their magnetic properties. Translation of this therapeutic approach into the clinic will be more accessible because of its compatibility with this relevant imaging modality. They can also be labeled with other imaging reporters such as a Cy5.5 near-infrared optical dye for correlative optical imaging and fluorescence microscopy. Here, we demonstrate that nanoparticles labeled with Cy5.5 and conjugated to therapeutic oligomers targeting oncogenic miRNA-10b (termed MN-anti-miR10b, or "nanodrug") administered intravenously accumulate in metastatic sites, opening a possibility for therapeutic intervention of metastatic breast cancer.
转移性乳腺癌是一种破坏性疾病，治疗选择非常有限，需要新的治疗策略。致癌 miRNA 已被证明与乳腺癌的转移潜能有关，并与肿瘤细胞的迁移、侵袭和存活有关。然而，将抑制性 RNA 分子递送到靶组织可能很困难。为了克服这一挑战并向肿瘤输送有效的反义寡核苷酸，我们利用磁性氧化铁纳米颗粒作为递送平台。这些纳米颗粒靶向血管通透性增加的组织，如炎症或癌症部位。由于其磁性，这些纳米颗粒的递送可以通过磁共振成像 (MRI) 在体内进行监测。由于其与这种相关成像方式的兼容性，这种治疗方法在临床上更容易实现。它们还可以用其他成像报告器标记，例如 Cy5.5 近红外光学染料，用于相关的光学成像和荧光显微镜。在这里，我们证明了用 Cy5.5 标记并与针对致癌 miRNA-10b 的治疗性寡核苷酸缀合的纳米颗粒（称为 MN-anti-miR10b，或“纳米药物”）经静脉内给药后会在转移部位积聚，为治疗转移性乳腺癌提供了一种可能的治疗干预方法。
