Imaging was conducted at different time points including preinjection, 12, 24, and 48 hours postinjection. nanoparticles. ijn-13-6809s3.tif (7.7M) GUID:?B8F27B56-8477-4FAD-8D82-9AD4B017C5F1 Abstract Purpose Early diagnosis and therapy are essential to improve the prognosis of patients with pancreatic cancer. However, standard imaging does not significantly increase the capability to detect early stage disease. In this study, we developed a multifunctional theranostic nanoplatform for accurate analysis and effective treatment of pancreatic malignancy. Methods We developed a theranostic nanoparticle (NP) based on platinum nanocages (AuNCs) revised 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 launch effectiveness in vitro. Near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) and restorative capabilities were tested in vitro and in vivo. Results ORI-GPC1-NPs shown 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- bad). Compared with ORI and ORI-NPs, ORI-GPC1-NPs significantly inhibited the viability and enhanced the apoptosis of pancreatic malignancy 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. Summary ORI-GPC1-NP is definitely a encouraging Rabbit Polyclonal to TMEM101 theranostic platform for the simultaneous analysis and effective treatment of pancreatic malignancy. strong class=”kwd-title” Keywords: pancreatic malignancy, GPC1, ORI, theranostic Intro Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of global morbidity and mortality, having a 5-yr survival 5%.1 The very low survival rate is mainly due to the lack of early analysis and effective treatment strategies.2,3 Although existing imaging systems can provide morphological information about pancreatic cells, single-modality imaging does not have sufficient level of sensitivity and specificity for the analysis of pancreatic malignancy.4 Multimodal imaging for pancreatic cancer offered a more comprehensive look at of tumor cells.5 A major concern in treatment is that PDAC is not sensitive to traditional chemotherapy.6,7 Major problems in clinical antitumor therapy include the short half-life, hydrophobic nature, undesired adverse effects, and poor bioavailability.8 Therefore, a new strategy that combines multimodal imaging analysis and targeted therapy is urgently needed to eliminate pancreatic cancer. Molecular imaging gives a promising approach to combine multimodal imaging analysis and targeted therapy to improve analysis and effectiveness of pancreatic malignancy.9,10 Platinum nanocages (AuNCs) are widely used in cancer theranostics because of the easy modification, excellent stability, and biocompatibility.11 AuNCs have unique properties such as the inner hollow space,12 ease of surface functionalization,13 and the capacity to transport and deliver numerous cargo.14 By loading a variety of functional materials such as dyes, imaging providers, or medicines, AuNCs can achieve multimodal imaging analysis and targeted therapy. Armin et al developed PEGylated gold-mitoxantrone nanoparticles (NPs) and found that it could improve the therapy effectiveness of malignancy.15 Compared with a single-function gold NP drug delivery system, a multifunctional theranostic nanoplatform is capable of multimodal imaging diagnosis and targeted treatment of cancer. Earlier studies describe that theranostic providers are combined with diagnostic elements and therapeutic providers for pancreatic malignancy imaging and treatment.16 Deng et al developed an mesothelin-targeted NP for magnetic resonance imaging (MRI) and targeted therapy.17 Wang et al reported a gemcitabine (GEM)-loaded nanospheres for MRI and thermochemotherapy.18 Jaidev et al reported human epidermal growth factor receptor-targeted multifunctional NP for imaging and treatment of pancreatic cancer.19 However, these studies only offered single-modality imaging to image pancreatic cancer. In this study, we constructed a multifunctional theranostic nanoplatform Almitrine mesylate capable of multimodal imaging analysis and targeted therapy for pancreatic malignancy. The platform offers these characteristics. First, it uses glypican-1 (GPC1) as the theranostic target. Targeting changes of NPs can enhance the build up of NPs in tumor sites. GPC1 is definitely a Almitrine mesylate member of the heparan sulfate proteoglycan family and covalently anchored to the extracytoplasmic surface of the plasma membrane.20 GPC1 takes on an important part in cancer progression by influencing tumor metastasis, invasion, and apoptosis. It is Almitrine mesylate selectively overexpressed in pancreatic malignancy,21,22 but not in normal pancreatic tissues, pancreatic tissues, or benign pancreatic tumors.23 However, to date, this molecule has rarely been used as a target for pancreatic cancer molecular imaging. Oridonin (ORI) is usually a tetracycline diterpenoid compound that is naturally found in em Rabdosia rubescens /em .24 It has detoxification, antibacterial, anti-inflammatory, and anti- tumor effects.25,26 Unlike synthetic chemical drugs, ORI is an inexpensive natural compound.
Imaging was conducted at different time points including preinjection, 12, 24, and 48 hours postinjection