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聚乙二醇包覆的氧化铁纳米颗粒整合促黄体生成素释放激素靶向磁热疗和阿霉素用于肺癌和乳腺癌细胞的体外评估

In vitro assessment of polyethylene glycol-coated iron oxide nanoparticles integrating luteinizing hormone releasing-hormone targeted magnetic hyperthermia and doxorubicin for lung and breast cancer cells.

作者信息

Srivastava Neha, Chudasama Bhupendra, Baranwal Manoj

机构信息

Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, India.

School of Physics and Materials Science, Thapar Institute of Engineering and Technology, Patiala 147004, India.

出版信息

Biointerphases. 2025 May 1;20(3). doi: 10.1116/6.0004228.

Abstract

Magnetic nanoparticle-based targeted hyperthermia, combined with chemotherapy, is a promising approach for cancer treatment. In this study, a targeted magnetic drug delivery system was developed, comprising doxorubicin (DOX), a [D-Trp6] luteinizing hormone-releasing hormone (LHRH) (Triptorelin) ligand, and a polyethylene glycol (PEG)-coated magnetite core, aiming to enhance cancer therapy efficacy. Fourier-transform infrared spectroscopy confirmed the conjugation of LHRH onto the PEG-coated Fe3O4 nanoparticles. Ultraviolet-visible spectroscopy was employed to assess drug loading, revealing a loading efficiency of 66%. The DOX-loaded, LHRH-tagged PEG-coated Fe3O4 nanoparticles were evaluated for their cytotoxic effects on A549 and MCF-7 cancer cell lines under three treatment modalities: thermotherapy, chemotherapy, and combined thermo-chemotherapy, both with and without the application of a magnetic field. Cell viability was assessed using the 2,5-diphenyltetrazolium bromide (MTT) assay. In A549 cells, the combined thermo-chemotherapy treatment at a DOX concentration of 10 μg/ml resulted in an 88% reduction in cell viability, outperforming chemotherapy alone (62%) and thermotherapy alone (47%). Similarly, in MCF-7 cells, the combined treatment at 8 μg/ml DOX led to a 91% reduction in viability, surpassing the effects of chemotherapy (57%) and thermotherapy (45%) individually. Additionally, the targeted DOX-loaded nanoparticles significantly elevated interferon-gamma production, indicating an enhanced immune response and increased cancer cell apoptosis.

摘要

基于磁性纳米颗粒的靶向热疗联合化疗是一种很有前景的癌症治疗方法。在本研究中,开发了一种靶向磁性药物递送系统,其由阿霉素(DOX)、一种[D-色氨酸6]促黄体生成素释放激素(LHRH)(曲普瑞林)配体和一个聚乙二醇(PEG)包覆的磁铁矿核心组成,旨在提高癌症治疗效果。傅里叶变换红外光谱证实了LHRH与PEG包覆的Fe3O4纳米颗粒的结合。采用紫外可见光谱法评估药物负载量,结果显示负载效率为66%。对负载DOX、带有LHRH标记的PEG包覆的Fe3O4纳米颗粒在三种治疗方式下对A549和MCF-7癌细胞系的细胞毒性作用进行了评估:热疗、化疗以及联合热化疗,分别在施加和不施加磁场的情况下。使用2,5-二苯基四氮唑溴盐(MTT)法评估细胞活力。在A549细胞中,DOX浓度为10μg/ml时的联合热化疗导致细胞活力降低88%,优于单独化疗(62%)和单独热疗(47%)。同样,在MCF-7细胞中,DOX浓度为8μg/ml时的联合治疗导致活力降低91%,超过了单独化疗(57%)和单独热疗(45%)的效果。此外,负载DOX的靶向纳米颗粒显著提高了γ干扰素的产生,表明免疫反应增强且癌细胞凋亡增加。

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