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Targeting Glut1-overexpressing MDA-MB-231 cells with 2-deoxy-D-g1ucose modified SPIOs
Xiu Hong Shan1, Hui Hu, Fei Xiong
1Department of Radiology, The Affiliated Renmin Hospital, Jiangsu University, Zhenjiang, Jiangsu 212002, China. xhongshan@hotmail.com
Abstract:
Glucose transporter (Glut), a cellular transmembrane receptor, plays a key role in cell glucose metabolism and is linked to a poor prognosis in various human cancers. In this study, we prepared γ-Fe(2)O(3) NPs coated with DMSA, in which modified with 2-DG, then γ-Fe(2)O(3)@DMSA-DG NPs was constructed. The specific interactions between Glut1-overexpressing tumor cells (MDA-MB-231) and γ-Fe(2)O(3)@DMSA-DG NPs were observed using Prussian blue staining and transmission electron microscope (TEM), and found that γ-Fe(2)O(3)@DMSA-DG NPs were absorbed targetedly by the cells. Furthermore, the capacity of transporting SPIOs into tumor cells using these γ-Fe(2)O(3)@DMSA-DG NPs was evaluated with a 1.5 T clinical magnetic resonance imaging (MRI) scanner. It was found that the acquired MRI T2 signal intensity of MDA-MB-231 cells that were treated with the γ-Fe(2)O(3)@DMSA-DG NPs decreased significantly, and it was inhibited by competition with antibody of Glut1. Our results suggest that γ-Fe(2)O(3)@DMSA-DG NPs are a useful targeting to Glut1-overexpressing tumor cells in vitro and that γ-Fe(2)O(3)@DMSA-DG NPs may serve as a MRI-targeted tumor agent for better tumor imaging.
Insights
Superparamagnetic iron oxide nanoparticles (SPIONs) modified with 2-deoxyglucose (2-DG) target glucose transporter 1 (Glut1)-overexpressing cancer cells. These targeted nanoparticles show potential for improved MRI-based tumor imaging and diagnosis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Glucose transporter (Glut) is crucial for cell metabolism and linked to poor cancer prognosis.
- Targeting Glut1 offers a strategy for cancer diagnosis and therapy.
Purpose of the Study:
- To construct and evaluate novel γ-Fe(2)O(3)@DMSA-2-DG nanoparticles (NPs) for targeted delivery to Glut1-overexpressing tumor cells.
- To assess the potential of these NPs as contrast agents for magnetic resonance imaging (MRI).
Main Methods:
- Synthesis of γ-Fe(2)O(3)@DMSA-2-DG NPs.
- Assessment of NP interaction with Glut1-overexpressing MDA-MB-231 cells using Prussian blue staining and TEM.
- Evaluation of MRI T2 signal changes in treated cells using a 1.5 T MRI scanner.
- Competition assay with Glut1 antibody to confirm targeting specificity.
Main Results:
- γ-Fe(2)O(3)@DMSA-2-DG NPs were successfully constructed and showed specific uptake by Glut1-overexpressing MDA-MB-231 cells.
- Targeted delivery of NPs resulted in a significant decrease in MRI T2 signal intensity.
- The observed MRI signal reduction was inhibited by competition with Glut1 antibody, confirming targeted uptake.
Conclusions:
- γ-Fe(2)O(3)@DMSA-2-DG NPs demonstrate effective targeting of Glut1-overexpressing tumor cells in vitro.
- These NPs hold promise as a novel MRI-targeted contrast agent for enhanced tumor imaging.