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IgG 抗体介导的金纳米颗粒偶联甲氨蝶呤作为肺癌靶向化疗

英文原题:IgG antibodies mediated gold nanoparticles conjugated to methotrexate as targeted chemotherapy for lung cancer.

查看英文原题

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

PubMed 2023/12/01(内容时间) Artif Cells Nanomed Biotechnol Q1 · IF 5.6(JCR 2025)

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中文摘要

长春胺作为一种天然化学物质,在IgG抗体介导的生物金纳米颗粒(IgGAuNPs)的合成中被用作还原剂。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同种型可通过多态性Fcγ受体(FcγRs)靶向癌细胞并具有治疗作用。它们可通过抑制不同的细胞内信号转导通路来限制细胞分裂,并分别通过抗体依赖性细胞介导的细胞毒作用和巨噬细胞介导的抗体依赖性吞噬作用激活NK细胞和巨噬细胞。

此外,通过物理技术对IgGAuNPs和MTX-IgGAuNPs进行了表征。而且,在IgGAuNPs合成过程中及合成后,通过荧光光谱分析了IgG结构中的3D构象变化。

此外,IgGAuNPs和MTX-IgGAuNPs对肺癌(A549细胞)有效,同时对正常细胞(NRK细胞)无毒。通过MTT细胞毒性试验、DCFDA法检测ROS产生以及线粒体释放Cyt-c以介导caspase-3依赖性凋亡,检测了IgGAuNPs和MTX-IgGAuNPs的有效性。

此外,在DAPI试验下检测了颗粒内化进入细胞核的确认,发现颗粒引起核碎裂,这也是凋亡的一个指征。

展开英文摘要原文

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.

论文信息

作者
Syed A、Baker A、Mohany M、Elgorban AM、Khan MS、Al-Rejaie SS
第一作者单位
Department of Botany and Microbiology, College of Science, King Saud University, P.O. 2455, Riyadh 11451, Saudi Arabia.Saudi Arabia
通讯作者单位
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. 55760, Riyadh 11451, Saudi Arabia.Saudi Arabia
期刊
Artificial cells, nanomedicine, and biotechnology2023 Dec
原文标识
PubMed 37548440 · DOI 10.1080/21691401.2023.2242419