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通过转铁蛋白包被的芳基化金纳米星增强阿霉素递送用于癌症治疗。

Enhanced delivery of doxorubicin via transferrin-coated arylated gold nanostars for cancer therapy.

作者信息

Hameed Mehavesh K, Gul Muhammad T, Khan Amir A, Kanu Gayathri A, AbuOdeh Raed O, Kim Sanghyeon, Han Changseok, Mohamed Ahmed A

机构信息

Center for Advanced Materials Research, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates.

Human Genetics and Stem Cells Research Group, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates.

出版信息

Int J Pharm. 2025 Mar 30;673:125418. doi: 10.1016/j.ijpharm.2025.125418. Epub 2025 Feb 27.

Abstract

Transferrin protein-coated gold-aryl nanoparticles (TRF-AuNPs) and nanostars (TRF-AuNSs) were synthesized and characterized. The water-dispersible gold-aryl nanoparticles and nanostars covalently functionalized with a -CH-4-COOH organic shell were synthesized from an aryldiazonium gold(III) salt. TRF-AuNPs had an average size of 10.5 ± 5.6 nm, and TRF-AuNSs had an average size of 177.4 ± 31.3 nm, as obtained with transmission electron microscopy. The zeta potential values indicated a positive surface charge of + 35 mV for both bioconjugates, indicating successful functionalization. An MTT assay was performed to investigate the cytotoxicity of TRF-AuNSs, which was confirmed to be non-toxic in the MDA-MB-231 breast cancer cell line. Cellular uptake was analyzed using flow cytometry and confocal microscopy. TRF was chosen to functionalize gold-aryl NPs and gold-aryl NSs because of the overexpression of its receptors on cancer cells. The efficiency of TRF-AuNSs was investigated, and the TRF protein receptor expression on cancer cells was probed using polymerase chain reaction (PCR). The antiproliferative effects of the doxorubicin drug (Dox) were assessed; the gold nanomaterials were evaluated as efficient carriers for the anticancer drug Dox. Dox-coated TRF-gold nanomaterials induced apoptosis and necrosis via DNA damage and increased ROS levels, as confirmed by flow cytometry and spectrofluorometry. Our study supports the significance of the shape of gold nanomaterials in Dox drug delivery to cancer cells.

摘要

合成并表征了转铁蛋白包被的金-芳基纳米颗粒(TRF-AuNPs)和纳米星(TRF-AuNSs)。由芳基重氮金(III)盐合成了用-CH₂-4-COOH有机壳共价功能化的水分散性金-芳基纳米颗粒和纳米星。通过透射电子显微镜观察,TRF-AuNPs的平均尺寸为10.5±5.6nm,TRF-AuNSs的平均尺寸为177.4±31.3nm。zeta电位值表明两种生物共轭物的表面带正电荷,为+35mV,表明功能化成功。进行MTT试验以研究TRF-AuNSs的细胞毒性,证实其在MDA-MB-231乳腺癌细胞系中无毒。使用流式细胞术和共聚焦显微镜分析细胞摄取情况。由于其受体在癌细胞上的过表达,选择转铁蛋白对金-芳基纳米颗粒和金-芳基纳米星进行功能化。研究了TRF-AuNSs的效率,并使用聚合酶链反应(PCR)探测癌细胞上TRF蛋白受体的表达。评估了阿霉素(Dox)的抗增殖作用;评估了金纳米材料作为抗癌药物Dox的有效载体。经流式细胞术和荧光光谱法证实,Dox包被的TRF-金纳米材料通过DNA损伤和增加ROS水平诱导细胞凋亡和坏死。我们的研究支持了金纳米材料的形状在Dox药物递送至癌细胞中的重要性。

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