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聚多巴胺包覆的 Au-Ag 纳米颗粒引导的多细胞死亡通路光热治疗结直肠癌。

Polydopamine-coated Au-Ag nanoparticle-guided photothermal colorectal cancer therapy through multiple cell death pathways.

机构信息

Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

出版信息

Acta Biomater. 2019 Jan 1;83:414-424. doi: 10.1016/j.actbio.2018.10.032. Epub 2018 Oct 24.

DOI:10.1016/j.actbio.2018.10.032
PMID:30366131
Abstract

Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP-mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100 μg in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells.

摘要

纳米颗粒因其高稳定性、精确靶向性和高生物相容性而成为一种新的治疗模式。具有聚多巴胺涂层的支化 Au-Ag 纳米颗粒(Au-Ag@PDA)具有很强的近红外吸收能力,无细胞毒性,但光热转换效率高。然而,Au-Ag@PDA 在体内和体外的光热活性尚未被报道,光热纳米材料的作用机制也不清楚。因此,在本研究中,使用结直肠癌细胞系 HCT-116 和裸鼠异种移植瘤来观察 Au-Ag@PDA 在体内和体外的光热效应。结果表明,Au-Ag@PDA NPs 显著抑制结直肠癌细胞的增殖并诱导其凋亡。此外,Au-Ag@PDA NP 介导的光热治疗在体内 50 和 100μg 剂量下抑制肿瘤生长。Au-Ag@PDA NPs 诱导结直肠癌细胞死亡的机制涉及多种途径,包括 caspase 依赖性和非依赖性凋亡、线粒体损伤、溶酶体膜通透性和自噬。因此,我们的研究结果表明,Au-Ag@PDA NPs 可作为光热消融结直肠癌细胞的潜在抗肿瘤药物。

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