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LHRH 缀合的 PEG 包覆磁铁矿纳米颗粒增强细胞摄取,用于三阴性乳腺癌细胞的特异性靶向。

Enhanced cellular uptake of LHRH-conjugated PEG-coated magnetite nanoparticles for specific targeting of triple negative breast cancer cells.

机构信息

Department of Mechanical and Aerospace Engineering, Princeton University, Olden Street, Princeton, NJ 08544, USA; Princeton Institute of Science and Technology of Materials (PRISM), Princeton University, 70 Prospect Street, Princeton, NJ 08544, USA.

Department of Mechanical and Aerospace Engineering, Princeton University, Olden Street, Princeton, NJ 08544, USA; Princeton Institute of Science and Technology of Materials (PRISM), Princeton University, 70 Prospect Street, Princeton, NJ 08544, USA; Department of Mechanical Engineering, Higgins Lab, 100 Institute Road, Worcester Polytechnic Institute (WPI), Worcester, MA 01609, USA.

出版信息

Mater Sci Eng C Mater Biol Appl. 2018 Jul 1;88:32-45. doi: 10.1016/j.msec.2018.02.017. Epub 2018 Mar 30.

Abstract

Targeted therapy is an emerging technique in cancer detection and treatment. This paper presents the results of a combined experimental and theoretical study of the specific targeting and entry of luteinizing hormone releasing hormone (LHRH)-conjugated PEG-coated magnetite nanoparticles into triple negative breast cancer (TNBC) cells and normal breast cells. The conjugated nanoparticles structures, cellular uptake of PEG-coated magnetite nanoparticles (MNPs) and LHRH-conjugated PEG-coated magnetite nanoparticles (LHRH-MNPs) into breast cancer cells and normal breast cells were investigated using a combination of transmission electron microscope, optical and confocal fluorescence microscopy techniques. The results show that the presence of LHRH enhances the uptake of LHRH-MNPs into TNBC cells. Nanoparticle entry into breast cancer cells is also studied using a combination of thermodynamics and kinetics models. The trends in the predicted nanoparticle entry times (into TNBC cells) and the size ranges of the engulfed nanoparticles (within the TNBC cells) are shown to be consistent with experimental observations. The implications of the results are then discussed for the specific targeting of TNBCs with LHRH-conjugated PEG-coated magnetite nanoparticles for the early detection and treatment of TNBC.

摘要

靶向治疗是癌症检测和治疗中的一种新兴技术。本文介绍了黄体生成素释放激素(LHRH)缀合聚乙二醇(PEG)涂层磁铁矿纳米粒子特异性靶向和进入三阴性乳腺癌(TNBC)细胞和正常乳腺细胞的实验和理论研究结果。使用透射电子显微镜、光学和共聚焦荧光显微镜技术的组合,研究了共轭纳米粒子结构、PEG 涂层磁铁矿纳米粒子(MNPs)和 LHRH 缀合 PEG 涂层磁铁矿纳米粒子(LHRH-MNPs)进入乳腺癌细胞和正常乳腺细胞的摄取情况。结果表明,LHRH 的存在增强了 LHRH-MNPs 进入 TNBC 细胞的摄取。还使用热力学和动力学模型研究了纳米颗粒进入乳腺癌细胞的情况。预测的纳米颗粒进入时间(进入 TNBC 细胞)的趋势和被吞噬的纳米颗粒的尺寸范围(在 TNBC 细胞内)与实验观察结果一致。然后讨论了这些结果对 LHRH 缀合聚乙二醇(PEG)涂层磁铁矿纳米粒子对 TNBC 的特异性靶向用于 TNBC 的早期检测和治疗的意义。

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