研究动态
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以IgG抗体介导的金纳米颗粒结合甲氨蝶呤作为肺癌的靶向化疗。

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

发表日期:2023 Dec
作者: Asad Syed, Abu Baker, Mohamed Mohany, Abdallah M Elgorban, Mohd Sajid Khan, Salim S Al-Rejaie
来源: PHARMACOLOGY & THERAPEUTICS

摘要:

维肟碱是一种天然化学物质,在IgG抗体介导的生物源性金纳米颗粒(IgGAuNPs)的合成中被用作还原剂。最终,合成的IgGAuNPs与化疗药物甲氨喋呤(MTX-IgGAuNPs)进行生物偶联。IgG同型体可以通过多态性Fcγ受体(FcγRs)靶向癌细胞,并具有治疗效果。它们可以通过抑制不同的细胞内信号传导途径、通过抗体介导的细胞毒性和巨噬细胞介导的抗体吞噬作用激活NK细胞和巨噬细胞,从而限制细胞分裂。此外,IgGAuNPs和MTX-IgGAuNPs通过物理技术进行表征。此外,通过荧光光谱法分析IgG结构在IgGAuNPs的合成过程中和之后的三维构象变化。此外,IgGAuNPs和MTX-IgGAuNPs对肺癌(A549细胞)具有有效性,而对正常细胞(NRK细胞)无毒。通过MTT细胞毒性分析、DCFDA法检测ROS产生以及通过释放Cyt-c从线粒体诱导caspase-3介导的凋亡来检测IgGAuNPs和MTX-IgGAuNPs的有效性。此外,通过DAPI检测确认了颗粒物进入细胞核的现象,并发现颗粒物引起了核碎裂,这也是凋亡的一个指示。
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.