Enhancement of T2* weighted MRI imaging sensitivity of U87MG glioblastoma cells using γ-ray irradiated low molecular weight hyaluronic acid-conjugated iron nanoparticles

Haw Ming Huang, Ping Han Wu, Po Chien Chou, Wen Tien Hsiao, Hsin Ta Wang, Hsin Pei Chiang, Chi Ming Lee, Shwu Huey Wang, Yu Cheng Hsiao

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Introduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were pre- pared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection. Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co- precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs. Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA- IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells. Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.

原文英語
頁(從 - 到)3789-3802
頁數14
期刊International Journal of Nanomedicine
16
DOIs
出版狀態已發佈 - 2021

ASJC Scopus subject areas

  • 生物物理學
  • 生物工程
  • 生物材料
  • 藥學科學
  • 藥物發現
  • 有機化學

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