Oridonin-loaded and GPC1-targeted gold nanoparticles for multimodal imaging and therapy in pancreatic cancer.
Oridonin-loaded and GPC1-targeted gold nanoparticles for multimodal imaging and therapy in pancreatic cancer.
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装载冬凌草甲素、靶向 GPC1 的金纳米粒子用于胰腺癌的多模态成像和治疗
DOI：
10.2147/ijn.s177993
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发表时间：
2018
影响因子：
8
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Qiu W;Chen R;Chen X;Zhang H;Song L;Cui W;Zhang J;Ye D;Zhang Y;Wang Z
目的胰腺癌的早期诊断和治疗是改善预后的关键。然而，常规成像并不能显著提高检测早期疾病的能力。在这项研究中，我们开发了一种多功能治疗诊断纳米平台，用于胰腺癌的准确诊断和有效治疗。方法我们开发了一种基于透明质酸（HA）修饰的金纳米笼（AuNCs）的治疗诊断纳米颗粒（NP），并与抗磷脂酰肌醇蛋白聚糖-1（GPC 1）抗体、冬凌草甲素（ORI）、钆（Gd）和Cy 7染料偶联。我们评估了GPC 1-Gd-ORI@ HAuNCs-Cy 7 NP（ORI-GPC 1-NP）的特征，包括形态、流体动力学尺寸、稳定性和表面化学品。并测定了载药量和体外释药效率。在体外和体内测试了近红外荧光（NIRF）/磁共振成像（MRI）和治疗能力。结果ORI-GPC 1-NPs具有长期稳定性和荧光/MRI特性。生物透射电子显微镜（bio-TEM）成像显示，ORI-GPC 1-NPs被内吞到PANC-1和BXPC-3（过表达GPC 1）中，但不在293 T细胞（GPC 1阴性）中。与ORI和ORI-NPs相比，ORI-GPC 1-NPs在体外能显著抑制胰腺癌细胞的存活率并促进其凋亡。此外，血液测试表明ORI-GPC 1-NP显示出可忽略的毒性。体内研究表明，ORI-GPC 1-NPs能够在胰腺肿瘤异种移植小鼠中实现多模式成像和靶向治疗。结论ORI-GPC 1-NP是一种很有前途的胰腺癌诊断和治疗诊断平台。
Purpose Early diagnosis and therapy are critical to improve the prognosis of patients with pancreatic cancer. However, conventional imaging does not significantly increase the capability to detect early stage disease. In this study, we developed a multifunctional theranostic nanoplatform for accurate diagnosis and effective treatment of pancreatic cancer. Methods We developed a theranostic nanoparticle (NP) based on gold nanocages (AuNCs) modified with hyaluronic acid (HA) and conjugated with anti-Glypican-1 (anti-GPC1) antibody, oridonin (ORI), gadolinium (Gd), and Cy7 dye. We assessed the characteristics of GPC1-Gd-ORI@HAuNCs-Cy7 NPs (ORI-GPC1-NPs) including morphology, hydrodynamic size, stability, and surface chemicals. We measured the drug loading and release efficiency in vitro. Near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) and therapeutic capabilities were tested in vitro and in vivo. Results ORI-GPC1-NPs demonstrated long-time stability and fluorescent/MRI properties. Bio-transmission electron microscopy (bio-TEM) imaging showed that ORI-GPC1-NPs were endocytosed into PANC-1 and BXPC-3 (overexpression GPC1) but not in 293 T cells (GPC1- negative). Compared with ORI and ORI-NPs, ORI-GPC1-NPs significantly inhibited the viability and enhanced the apoptosis of pancreatic cancer cells in vitro. Moreover, blood tests suggested that ORI-GPC1-NPs showed negligible toxicity. In vivo studies showed that ORI-GPC1-NPs enabled multimodal imaging and targeted therapy in pancreatic tumor xenografted mice. Conclusion ORI-GPC1-NP is a promising theranostic platform for the simultaneous diagnosis and effective treatment of pancreatic cancer.