Folate‑targeted polymeric micelles loaded with superparamagnetic iron oxide as a contrast agent for magnetic resonance imaging of a human tongue cancer cell line

Cui,Min‑Yi; Dong,Zhi; Cai,Huasong; Huang,Kun; Liu,Yi; Fang,Zhuangnian; Li,Xiangmin; Luo,Yanji

doi:10.3892/mmr.2017.7565

Folate‑targeted polymeric micelles loaded with superparamagnetic iron oxide as a contrast agent for magnetic resonance imaging of a human tongue cancer cell line

Authors:
- Min‑Yi Cui
- Zhi Dong
- Huasong Cai
- Kun Huang
- Yi Liu
- Zhuangnian Fang
- Xiangmin Li
- Yanji Luo
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Affiliations: Department of Radiology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat‑Sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong 510055, P.R. China, Department of Radiology, The First Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: September 20, 2017 https://doi.org/10.3892/mmr.2017.7565
Pages: 7597-7602

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Abstract

The aim of the present study was to investigate the feasibility of using folate‑targeted superparamagnetic iron oxide nanoparticles (SPIO) as a magnetic resonance (MR) contrast agent that targets human tongue cancer cells. Folate‑targeted and folate‑free bilayer micelles composed of a diblock copolymer of polyethylene glycol (PEG) and poly‑caprolactone (PCL) that encapsulated SPIO in their hydrophobic core (SPIO‑PEG‑PCL micelles) were synthesized. The cytotoxicity of each set of micelles towards Tca‑8113 cells was examined using methyl thiazolyl tetrazolium (MTT) assays. Tca‑8113 cells were incubated with folate‑free SPIO‑PEG‑PCL micelles and folate‑targeted SPIO‑PEG‑PCL micelles at an Fe concentration of 80 µg/ml for 0.5, 1 and 2 h. MR imaging was subsequently performed and relative T2 relaxation time was recorded. Endocytosis of each micelle type was observed using Prussian blue staining. The MTT assays demonstrated that varying concentrations of folate‑targeted SPIO‑PEG‑PCL micelles did not result in statistically significant differences in Tca‑8113 cell viability when compared with folate‑free SPIO‑PEG‑PCL micelles (F=0.698; P=0.676). In the MR images obtained, decreased T2‑weighted signal intensity was observed for the folate‑targeted SPIO‑PEG‑PCL and folate‑free SPIO‑PEG‑PCL micelle treatments, particularly after the 2‑h incubation period. However, the folate‑targeted micelles exhibited a significantly greater decrease in signal intensity and a higher relative T2 relaxation time at each time point (P=0.002). In addition, blue intracellular particles were observed in the cells that were incubated with each type of micelle and stained with Prussian blue. However, a greater number of blue particles underwent endocytosis in the folate‑targeted group. Thus, folate‑targeted SPIO‑PEG‑PCL micelles exhibited preferential targeting of Tca‑8113 cells when compared with folate‑free SPIO‑PEG‑PCL micelles, and these results support the potential for these micelles to be used for the early diagnosis of tongue cancer.

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