Precision Health Program, Michigan State University; Department of Biomedical Engineering, College of Engineering, Michigan State University.
Precision Health Program, Michigan State University; Department of Radiology, College of Human Medicine, Michigan State University.
J Vis Exp. 2024 Sep 27(211). doi: 10.3791/66986.
Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain malignancy for which there is no cure. The blood-brain barrier is a significant hurdle in the delivery of therapies to GBM. Reported here is an image-guided, iron oxide-based therapeutic delivery nano platform capable of bypassing this physiological barrier by virtue of size and accumulating in the tumor region, delivering its payload. This 25 nm nano platform consists of crosslinked dextran-coated iron oxide nanoparticles labeled with Cy5.5 fluorescent dye and containing antisense oligonucleotide as a payload. The magnetic iron oxide core enables tracking of the nanoparticles through in vivo magnetic resonance imaging, while Cy5.5 dye allows tracking by optical imaging. This report details the monitoring of the accumulation of this nanoparticle platform (termed MN-anti-miR10b) in orthotopically implanted glioblastoma tumors following intravenous injection. In addition, it provides insight into the in vivo delivery of RNA oligonucleotides, a problem that has hampered the translation of RNA therapeutics into the clinic.
多形性胶质母细胞瘤（GBM）是最常见且侵袭性最强的原发性脑恶性肿瘤，目前尚无治愈方法。血脑屏障是向 GBM 输送治疗药物的重大障碍。本文报道了一种基于氧化铁的、可成像引导的治疗性递药纳米平台，该平台可通过大小绕过这种生理屏障并在肿瘤区域聚集，从而传递其有效载荷。该 25nm 纳米平台由交联葡聚糖包裹的氧化铁纳米颗粒组成，这些纳米颗粒标记有 Cy5.5 荧光染料，并包含作为有效载荷的反义寡核苷酸。磁性氧化铁核心可通过体内磁共振成像追踪纳米颗粒，而 Cy5.5 染料则可通过光学成像进行追踪。本报告详细介绍了静脉注射后这种纳米颗粒平台（称为 MN-anti-miR10b）在原位植入的胶质母细胞瘤肿瘤中的积累情况。此外，本报告还深入探讨了 RNA 寡核苷酸的体内递药问题，这一问题一直阻碍着 RNA 疗法在临床上的应用。
