The First Clinical Medical School, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Int J Nanomedicine. 2018 Oct 24;13:6809-6827. doi: 10.2147/IJN.S177993. eCollection 2018.
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.
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.
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.
ORI-GPC1-NP is a promising theranostic platform for the simultaneous diagnosis and effective treatment of pancreatic cancer.
早期诊断和治疗对于改善胰腺癌患者的预后至关重要。然而，常规成像并不能显著提高早期疾病的检测能力。在本研究中，我们开发了一种多功能治疗性纳米平台，用于胰腺癌的精确诊断和有效治疗。
我们开发了一种基于金纳米笼（AuNCs）的治疗性纳米粒子（NP），该纳米笼经透明质酸（HA）修饰，并与抗 GPC1 抗体、冬凌草甲素（ORI）、钆（Gd）和 Cy7 染料结合。我们评估了 GPC1-Gd-ORI@HAuNCs-Cy7 NPs（ORI-GPC1-NPs）的特性，包括形态、水动力粒径、稳定性和表面化学性质。我们测量了体外的药物负载和释放效率。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。
ORI-GPC1-NPs 表现出长时间的稳定性和荧光/MRI 特性。生物透射电子显微镜（bio-TEM）成像显示，ORI-GPC1-NPs 被内吞到 PANC-1 和 BXPC-3（过表达 GPC1）细胞中，但 293 T 细胞（GPC1-阴性）中没有。与 ORI 和 ORI-NPs 相比，ORI-GPC1-NPs 显著抑制了体外胰腺癌细胞的活力并增强了其凋亡。此外，血液测试表明 ORI-GPC1-NPs 表现出可忽略的毒性。体内研究表明，ORI-GPC1-NPs 能够在胰腺癌异种移植小鼠中进行多模态成像和靶向治疗。
ORI-GPC1-NP 是一种有前途的治疗性纳米平台，可用于胰腺癌的同时诊断和有效治疗。
