Emodin-Conjugated PEGylation of Fe(3)O(4) Nanoparticles for FI/MRI Dual-Modal Imaging and Therapy in Pancreatic Cancer

BACKGROUND: Pancreatic cancer (PC) remains a difficult tumor to diagnose and treat. It is often diagnosed as advanced by reason of the anatomical structure of the deep retroperitoneal layer of the pancreas, lack of typical symptoms and effective screening methods to detect this malignancy, resulting in a low survival rate. Emodin (EMO) is an economical natural product with effective treatment and few side effects of cancer treatment. Magnetic nanoparticles (MNPs) can achieve multiplexed imaging and targeted therapy by loading a wide range of functional materials such as fluorescent dyes and therapeutic agents. PURPOSE: The purpose of this study was to design and evaluate a multifunctional theranostic nanoplatform for PC diagnosis and treatment. METHODS: In this study, we successfully developed EMO-loaded, Cy7-functionalized, PEG-coated Fe(3)O(4) (Fe(3)O(4)-PEG-Cy7-EMO). Characteristics including morphology, hydrodynamic size, zeta potentials, stability, and magnetic properties of Fe(3)O(4)-PEG-Cy7-EMO were evaluated. Fluorescence imaging (FI)/magnetic resonance imaging (MRI) and therapeutic treatment were examined in vitro and in vivo. RESULTS: Fe(3)O(4)-PEG-Cy7-EMO nanoparticles had a core size of 9.9 ± 1.2 nm, which showed long-time stability and FI/MRI properties. Bio-transmission electron microscopy (bio-TEM) results showed that Fe(3)O(4)-PEG-Cy7-EMO nanoparticles were endocytosed into BxPC-3 cells, while few were observed in hTERT-HPNE cells. Prussian blue staining also confirmed that BxPC-3 cells have a stronger phagocytic ability as compared to hTERT-HPNE cells. Additionally, Fe(3)O(4)-PEG-Cy7-EMO had a stronger inhibition effect on BxPC-3 cells than Fe(3)O(4)-PEG and EMO. The hemolysis experiment proved that Fe(3)O(4)-PEG-Cy7-EMO can be used in vivo experiments. In vivo analysis demonstrated that Fe(3)O(4)-PEG-Cy7-EMO enabled FI/MRI dual-modal imaging and targeted therapy in pancreatic tumor xenografted mice. CONCLUSION: Fe(3)O(4)-PEG-Cy7-EMO may serve as a potential theranostic nanoplatform for PC.