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金纳米颗粒调节抗肿瘤分泌组,并对前列腺癌细胞具有强烈的细胞毒性作用。

Gold nanoparticles regulate the antitumor secretome and have potent cytotoxic effects against prostate cancer cells.

机构信息

Department of Urology, The First Hospital of Jilin University, Changchun, China.

Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.

出版信息

J Appl Toxicol. 2021 Aug;41(8):1286-1303. doi: 10.1002/jat.4117. Epub 2020 Dec 23.

Abstract

The specific cytotoxic effects of nanoparticles on tumor cells may be used in future antitumor clinical applications. Gold nanoparticles (AuNPs) have been reported to produce potent cytotoxic effects; however, the precise mechanism is unclear. In this study, AuNPs were synthesized; the average size of the particles was 62.2 ± 6 nm with smooth surface and multiple shapes, which were determined using transmission electron microscopy and field emission scanning electron microscopy. The selected area electron diffraction patterns suggested that the synthesized AuNPs were crystalline. The X-ray photoelectron spectroscopy (XPS) spectrum of the synthesized AuNPs has presented an intense peak at 100 eV, signifying the entire composition of Au in the developed AuNPs. This synthesized AuNPs showed the most potent efficacy in prostate cancer cells, regardless of whether or not they were androgen dependent. Secretome determinations using two-dimensional difference in-gel electrophoresis (2D-DIGE), followed by enzyme-linked immunosorbent assay and quantitative reverse transcriptase-polymerase chain reaction validations, have identified a series of secretory proteins that were dysregulated by AuNP treatment in prostate cancer cells, many of which are highly involved in cytokine-chemokine functions, including CXCL3, interleukin-10, CCL2, and matrix metalloproteinase 9 (MMP9). Further research on molecular mechanism has indicated that AuNPs can trigger the secretion of anticancer factors and myeloid cell-polarizing factors from tumor cells through MMP9 inhibition. These results have clearly signified the cytotoxic potential of AuNPs for treating prostate cancer and may provide a novel direction for prostate cancer therapy in the future.

摘要

纳米粒子对肿瘤细胞的特定细胞毒性作用可能用于未来的抗肿瘤临床应用。金纳米粒子(AuNPs)已被报道具有很强的细胞毒性作用,但确切的机制尚不清楚。在本研究中,合成了 AuNPs;使用透射电子显微镜和场发射扫描电子显微镜确定了颗粒的平均尺寸为 62.2±6nm,表面光滑,形状多样。选择区域电子衍射图案表明合成的 AuNPs 是结晶的。合成的 AuNPs 的 X 射线光电子能谱(XPS)谱在 100eV 处呈现出强烈的峰,表明所开发的 AuNPs 中 Au 的全部组成。该合成的 AuNPs 对前列腺癌细胞具有最强的功效,无论其是否依赖雄激素。使用二维差异凝胶电泳(2D-DIGE)进行的分泌组测定,随后进行酶联免疫吸附测定和定量逆转录聚合酶链反应验证,鉴定出一系列由 AuNP 处理在前列腺癌细胞中失调的分泌蛋白,其中许多高度参与细胞因子 - 趋化因子功能,包括 CXCL3、白细胞介素 10、CCL2 和基质金属蛋白酶 9(MMP9)。对分子机制的进一步研究表明,AuNPs 可以通过 MMP9 抑制触发肿瘤细胞分泌抗癌因子和髓样细胞极化因子。这些结果清楚地表明了 AuNPs 治疗前列腺癌的细胞毒性潜力,并可能为未来的前列腺癌治疗提供新的方向。

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