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金纳米颗粒偶联甲氨蝶呤 IgG 抗体介导的靶向化疗治疗肺癌。

IgG antibodies mediated gold nanoparticles conjugated to methotrexate as targeted chemotherapy for lung cancer.

机构信息

Department of Botany and Microbiology, College of Science, King Saud University, P.O. 2455, Riyadh 11451, Saudi Arabia.

Nanomedicine & Nanobiotechnology Lab, Department of Biosciences, Integral University, Lucknow, 226026 India.

出版信息

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):384-396. doi: 10.1080/21691401.2023.2242419.

Abstract

Vincamine, a natural chemical, was used as a reducing agent in the synthesis of IgG antibodies mediated biogenic gold nanoparticles (IgGAuNPs). Eventually, the synthesised IgGAuNPs were bioconjugated with the chemotherapeutic drug methotrexate (MTX-IgGAuNPs). The IgG isotype can target cancer cells through polymorphic Fc gamma receptors (FcγRs) and have therapeutic effects. They can restrict cell division by inhibiting different intracellular signal transduction pathways and activating NK cells and macrophages through antibody-dependent cellular cytotoxicity and macrophage-mediated antibody-dependent phagocytosis, respectively. Further, IgGAuNPs and MTX-IgGAuNPs were characterised by physical techniques. Moreover, 3D conformational changes in the structure of IgG were analysed by fluorescence spectroscopy during and after the synthesis of IgGAuNPs. Furthermore, the IgGAuNPs and MTX-IgGAuNPs were effective against lung cancer (A549 cells), while they were found to be non-toxic against normal cells (NRK cells). The effectiveness of IgGAuNPs and MTX-IgGAuNPs was examined by MTT cytotoxicity assay, DCFDA method for the production of ROS, and release of Cyt-c from the mitochondria for caspase-3-mediated apoptosis. Moreover, the confirmation of internalisation of particles into the nucleus was examined under the DAPI assay, and it was found that particles caused nuclear fragmentation, which was also an indication of apoptosis.

摘要

文拉辛,一种天然化学物质,被用作介导生物金纳米粒子(IgGAuNPs)合成的 IgG 抗体的还原剂。最终,合成的 IgGAuNPs 与化疗药物甲氨蝶呤(MTX-IgGAuNPs)进行了生物偶联。IgG 同种型可以通过多态性 Fcγ 受体(FcγRs)靶向癌细胞,并具有治疗作用。它们可以通过抑制不同的细胞内信号转导途径,以及通过抗体依赖性细胞毒性和巨噬细胞介导的抗体依赖性吞噬作用分别激活 NK 细胞和巨噬细胞,从而限制细胞分裂。此外,IgGAuNPs 和 MTX-IgGAuNPs 用物理技术进行了表征。此外,在合成 IgGAuNPs 期间和之后,通过荧光光谱分析了 IgG 结构的 3D 构象变化。此外,IgGAuNPs 和 MTX-IgGAuNPs 对肺癌(A549 细胞)有效,而对正常细胞(NRK 细胞)则无毒。通过 MTT 细胞毒性测定、ROS 产生的 DCFDA 方法以及细胞色素 c 从线粒体释放到 caspase-3 介导的凋亡来检查 IgGAuNPs 和 MTX-IgGAuNPs 的有效性。此外,通过 DAPI 测定检查了颗粒进入细胞核的内化确认,结果发现颗粒导致核碎裂,这也是细胞凋亡的一个迹象。

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