Journal Article

Oridonin-loaded and GPC1-targeted gold nanoparticles for multimodal imaging and therapy in pancreatic cancer

Chen, Rong, Zhang, Jingjing, Qiu, Wenli, Song, Lina, Ye, Dandan, Zhang, Huifeng, Zhang, Yifen, Chen, Xiao, Cui, Wenjing, Wang, Zhongqiu

2018

Overview

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.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove Medical Press
• Subject: Acids / Animals / Antibodies / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Apoptosis / Binding sites / Biocompatibility / Biomedical materials / Blood / Cancer / Cancer therapies / Care and treatment / Cell Cycle / Cell Line, Tumor / Cell Movement / Cell Survival / Diagnostic imaging / Diterpenes, Kaurane - therapeutic use / Drug Liberation / Enzymes / Glypicans - metabolism / Gold - chemistry / GPC1 / Health aspects / Heparan sulfate / Humans / Hyaluronic acid / Magnetic Resonance Imaging / Male / Medical examination / Medical prognosis / Medical research / Medicine / Medicine, Experimental / Metal Nanoparticles - chemistry / Metal Nanoparticles - ultrastructure / Mice, Inbred BALB C / Mice, Nude / Multimodal Imaging / Nanoparticles / NMR / Nuclear magnetic resonance / ORI / Original Research / Pancreatic cancer / Pancreatic Neoplasms - drug therapy / Pancreatic Neoplasms - pathology / Prognosis / T cells / Tetracycline / Tetracyclines / theranostic / Tumors / Viral antibodies