| Summary: | 碩士 === 國立臺灣大學 === 化學工程學研究所 === 96 === AC magnetic field induces magnetite nanoparticles (MNPs) to generate heat which could be used as heat source for hyperthermia, but poor targeting ability of MNPs to the tumor cells needs to be improved. To solve this problem, Trastuzumab, Herceptin®, a monoclonal antibody directed against the HER2/neu receptor overexpressed on breast tumor cell, was applied to this study. In this research, Trastuzumab was used as a targeting moiety to enhance the targeting ability of iron oxide nanoparticles.
The MNPs were synthesized by the coprecipitation method, and surface modification of MNPs was done by the poly(acrylic acid) (PAA) which not only prevents nanoparticles from aggregation but provides carboxyl groups for further synthesis. After the synthesis of PAA-coated MNP, the attachment of Herceptin was reached by the peptide bonding synthesis, N-hydroxysuccinimide (NHS) and 1-ethyl-3-[3-dimethylaminopropyl] -carbodiimide hydrochloride (EDC) methods. Furthermore, the basic properties of Herceptin-coated magnetite nanoparticles (HMNPs), such as particle size under different pH values, saturated magnetization and hyperthermia ability, were discussed. To further examine the targeting ability of HMNPs, the SK-BR3, human breast cancer cells were cultured with HMNPs, and inductive coupled plasma (ICP) was used to estimate the iron uptake amount. Additionally, the cytoxicity tests of HMNPs were achieved by in vitro test, in which human fibroblast served as normal cells.
From the FTIR spectrum, the antibody, Herceptin, was successfully attached onto the MNP surface due to the shift of C=O. Furthermore, the mass loss in TGA analysis gave identical conclusion. The particle size and saturated magnetization of HMNPs were 26 nm and 30 emu/g, respectively. ICP gave proof that HMNPs targeted human breast cancer cells with targeting efficiency about 2%. In vitro cytoxicity test showed the maximum tolerance concentration of HMNPs to human fibroblast was 0.05 mg/ml. The HMNPs are expected to achieve local hyperthermia for breast cancer therapy in future applications.
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