Application of Anigopep-2 Modified Iron-gold Alloy Nanoparticles in Brain Glioma MRI and Magnetic Hyperthermia Therapy

• Main Authors: Ching-Yu Kuo, 郭晉宇
• Other Authors: 鍾仁傑
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/u6r33b

碩士 === 國立臺北科技大學 === 化學工程與生物科技系生化與生醫工程碩士班 === 107 === In this study, iron-gold alloy nano-particles (Fe-Au NPs) were synthesized by thermal pyrolysis then surface-modified with brain-targeted peptide (Angiopep-2) for diagnosis and magnetic hyperthermia of glioma. The average particle size of the Fe-Au NPs and Ang-Fe-Au NPs were 6.44±0.94 nm and 6.72±1.1 nm; and the surface potential at pH 7 was -34.2±3.5 mV for Fe-Au NPs and -24.2±1.4 mV for Ang-FeAu NPs. Results of superconducting quantum interferometer tests revealed the superparamagnetism at room temperature (300 K) for the NPs. Under a magnetic field between ±20 kOe, the saturation magnetizations of Fe-Au NPs and Ang-Fe-Au NP were 5.4 emu/g and 5.6 emu/g respectively. Through magnetic resonance imaging (MRI) observation, it was found that both Fe-Au NPs and Ang-FeAu NPs could reduce the transverse relaxation time (T2) of water protons and they could serve as a MRI contrast agent. After heating a 50 mg/mL Fe-Au NPs solution with a high-frequency induction-heating machine (700 to 1100 kHz) for 600 s, the temperature rose to 42.1° C, and this convinced the NPs were suitable for application on cancer magnetic hyperthermia therapy. Results of the cytotoxicity test on mouse fibroblasts (L929) showed that Fe-Au NPs and Ang-FeAu NPs were not significantly toxic until 1 mg/mL. From the cytotoxicity test for glioma cells (C6) we found that at a concentration below 250 μg/mL the cell survival rate was above 80%. The nanomaterials are extremely biocompatible for L929, however, a concentration greater than 250 μg/mL starts to be hazard to C6 cells. Magnetic hyperthermia treatment of glioma cells was done using a high-frequency induction-heating machine with 40 μg/mL Fe-Au NPs or Ang-Fe-Au NPs. As heating time increased, the survival rate of cancer cells began to decrease. It was also observed that Ang-Fe-Au NPs led more cells to death than Fe-Au NPs. Images of biological transmission electron microscopy revealed that glioma cells endocytosed both Ang-Fe-Au NPs and Fe-Au NPs. The results of inductively coupled plasma optical emission spectrometry (ICP-OES) measurement showed that the uptake of Ang-Fe-Au NPs was 150% more than Fe-Au NPs after two hours treatment. Finally, the difference between the two groups before and after injection of Ang-Fe-Au NPs was observed by 7T MRI. It was found that two hours after injection of the Ang-Fe-Au NPs, the intensity of brightness for glioma tumor reduced. Ang-Fe-Au NPs can reduce the brain tumor size and prolong the survival time of living animals by Magnetic hyperthermia treatment. The above experimental results convinced Ang-Fe-Au NPs with excellent ability as a negative-acting agent and the potential in biomedical applications in diagnosis and treatment.