Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Nanomedicine. 2017 Nov;13(8):2451-2462. doi: 10.1016/j.nano.2017.08.007. Epub 2017 Aug 24.
In this work, a theranostic nanoparticle was developed for multimodal imaging and siRNA delivery. The core of the nanoparticles (NP) was formed by encapsulation of superparamagnetic iron oxides and indocyanine green in a PLGA matrix to serve as a multimodal probe for near-infrared (NIFR) and magnetic resonance (MR) imaging. The surface of the particle was coated with polyethylenimine (PEI) for siRNA delivery. Macrophages efficiently took up the nanoparticles and emitted strong NIFR and MR contrast. When transfected with siRNA targeting the pro-inflammatory enzyme cyclooxygenase-2 (COX-2), significant down-regulation of COX-2 was achieved in activated macrophages. Furthermore, after injection into a unilateral ureteral obstruction (UUO)-induced kidney injury model, NIFR and MRI imaging revealed accumulation of nanoparticles in the injury kidney. In addition, in vivo silencing of COX-2 was achieved by NP/PEI/siCOX-2, which further attenuated kidney injury. Our theranostic platform represents a promising approach for simultaneous diagnosis and treatment of inflammatory diseases.
在这项工作中，开发了一种治疗性纳米粒子，用于多模态成像和 siRNA 递送。纳米粒子（NP）的核心是通过将超顺磁性氧化铁和吲哚菁绿包封在 PLGA 基质中形成的，用作近红外（NIR）和磁共振（MR）成像的多模态探针。粒子的表面涂有聚乙烯亚胺（PEI）以递送 siRNA。巨噬细胞有效地摄取了纳米粒子，并发出强烈的 NIR 和 MR 对比。当用靶向促炎酶环加氧酶-2（COX-2）的 siRNA 转染时，在激活的巨噬细胞中 COX-2 的表达显著下调。此外，在单侧输尿管梗阻（UUO）诱导的肾损伤模型中注射后，NIR 和 MRI 成像显示纳米粒子在损伤肾脏中的积累。此外，NP/PEI/siCOX-2 实现了 COX-2 的体内沉默，进一步减轻了肾损伤。我们的治疗性平台代表了一种有前途的方法，用于炎症性疾病的同时诊断和治疗。
