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. 2021 Nov 6:16:7463-7478.
doi: 10.2147/IJN.S335588. eCollection 2021.

Emodin-Conjugated PEGylation of Fe3O4 Nanoparticles for FI/MRI Dual-Modal Imaging and Therapy in Pancreatic Cancer

Shuai Ren  1 , Lina Song  1 , Ying Tian  1 , Li Zhu  1 , Kai Guo  1 , Huifeng Zhang  1 , Zhongqiu Wang  1
Affiliations

Emodin-Conjugated PEGylation of Fe3O4 Nanoparticles for FI/MRI Dual-Modal Imaging and Therapy in Pancreatic Cancer

Shuai Ren et al. Int J Nanomedicine. .

Erratum in

Abstract

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 Fe3O4 (Fe3O4-PEG-Cy7-EMO). Characteristics including morphology, hydrodynamic size, zeta potentials, stability, and magnetic properties of Fe3O4-PEG-Cy7-EMO were evaluated. Fluorescence imaging (FI)/magnetic resonance imaging (MRI) and therapeutic treatment were examined in vitro and in vivo.

Results: Fe3O4-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 Fe3O4-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, Fe3O4-PEG-Cy7-EMO had a stronger inhibition effect on BxPC-3 cells than Fe3O4-PEG and EMO. The hemolysis experiment proved that Fe3O4-PEG-Cy7-EMO can be used in vivo experiments. In vivo analysis demonstrated that Fe3O4-PEG-Cy7-EMO enabled FI/MRI dual-modal imaging and targeted therapy in pancreatic tumor xenografted mice.

Conclusion: Fe3O4-PEG-Cy7-EMO may serve as a potential theranostic nanoplatform for PC.

Keywords: emodin; magnetic nanoparticles; pancreatic cancer; passive targeting.

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Conflict of interest statement

The authors report no conflicts of interest concerning this article.

Figures

Figure 1
Figure 1
Schematic illustration of the synthesis of Fe3O4-PEG-Cy7-EMO (A) and the possible mechanism of Fe3O4-PEG-Cy7-EMO enabled FI/MRI dual-modal imaging and targeted therapy in pancreatic tumor xenografted mice based on the EPR effect (B).
Figure 2
Figure 2
Characterization of NPs.
Figure 3
Figure 3
Fe3O4-PEG-Cy7-EMO enabled FI/MRI dual-modal imaging in vitro.
Figure 4
Figure 4
(A) The distribution of Fe3O4-PEG-Cy7-EMO in BxPC-3 and hTERT-HPNE cells examined by bio-TEM under 2 µm and 200 nm scale bars. (B) The distribution of Fe3O4-PEG-Cy7-EMO in BxPC-3 and hTERT-HPNE cells examined by Prussian Blue staining analysis.
Figure 5
Figure 5
(A) The MTT results of BxPC-3 and hTERT-HPNE cells incubated with Fe3O4-PEG, Fe3O4-PEG-Cy7-EMO, and EMO. (B) Apoptosis assays for BxPC-3 and hTERT-HPNE cells after different treatment. *P < 0.05 for Fe3O4-PEG vs Fe3O4-PEG-Cy7-EMO.
Figure 6
Figure 6
(A) The hemolysis experiments in vitro. Different treatments of tubes 1–5 are clarified in (B). (C) In vivo MRI images and (D) time-dependent intensity curves of Fe3O4-PEG and Fe3O4-PEG-Cy7-EMO groups. (E) In vivo fluorescence imaging and (F) ex vivo fluorescence imaging of hearts, livers, spleens, lungs, kidneys, and tumors.
Figure 7
Figure 7
(A) The H&E staining of different organs including hearts, livers, spleens, lungs, and kidneys. No obvious pathological changes were observed. (B) Prussian Blue staining analyses of ex vivo.
Figure 8
Figure 8
In vivo anti-tumor efficiency.
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