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表面修饰的碳点纳米颗粒与J774.1巨噬细胞的相互作用及细胞摄取

Interaction and cellular uptake of surface-modified carbon dot nanoparticles by J774.1 macrophages.

作者信息

Thoo Lester, Fahmi Mochamad Z, Zulkipli Ihsan N, Keasberry Natasha, Idris Adi

机构信息

PAPRSB Institute of Health Science, Universiti Brunei Darussalam, Brunei Darussalam.

Department of Chemistry, Universitas Airlangga, Indonesia.

出版信息

Cent Eur J Immunol. 2017;42(3):324-330. doi: 10.5114/ceji.2017.70978. Epub 2017 Oct 30.

Abstract

Carbon dot (Cdot) nanoparticles are an emerging class of carbon nanomaterials with a promising potential for drug delivery and bio imaging applications. Although the interaction between Cdots and non-immune cell types has been well studied, Cdot interactions with macrophages have not been investigated. Exposure of Cdot nanoparticles to J774.1 cells, a murine macrophage cell line, resulted in minimal toxicity, where notable toxicity was only seen with Cdot concentrations higher than 0.5 mg/ml. Flow cytometric analysis revealed that Cdots prepared from citric acid were internalized at significantly higher levels by macrophages compared with those prepared from bamboo leaves. Interestingly, macrophages preferentially took up phenylboronic acid (PB)-modified nanoparticles. By fluorescence microscopy, strong blue light-specific punctate Cdot fluorescence resembling Cdot structures in the cytosolic space was mostly observed in J774.1 macrophages exposed to PB-modified nanoparticles and not unmodified Cdot nanoparticles. PB binds to sialic acid residues that are overexpressed on diseased cell surfaces. Our findings demonstrate that PB-conjugated Cdots can be taken up by macrophages with low toxicity and high efficiency. These modified Cdots can be used to deliver drugs to suppress or eliminate aberrant immune cells such as macrophages associated with tumors such as tumor-associated macrophages.

摘要

碳点(Cdot)纳米颗粒是一类新兴的碳纳米材料,在药物递送和生物成像应用方面具有广阔的前景。尽管碳点与非免疫细胞类型之间的相互作用已得到充分研究,但碳点与巨噬细胞的相互作用尚未被研究。将碳点纳米颗粒暴露于小鼠巨噬细胞系J774.1细胞中,毒性极小,只有当碳点浓度高于0.5 mg/ml时才会出现明显毒性。流式细胞术分析表明,与竹叶制备的碳点相比,柠檬酸制备的碳点被巨噬细胞内化的水平显著更高。有趣的是,巨噬细胞优先摄取苯硼酸(PB)修饰的纳米颗粒。通过荧光显微镜观察,在暴露于PB修饰纳米颗粒而非未修饰碳点纳米颗粒的J774.1巨噬细胞中,大多观察到强烈的蓝光特异性点状碳点荧光,类似于胞质空间中的碳点结构。PB与患病细胞表面过度表达的唾液酸残基结合。我们的研究结果表明,PB偶联的碳点可以被巨噬细胞以低毒性和高效率摄取。这些修饰的碳点可用于递送药物,以抑制或消除异常免疫细胞,如与肿瘤相关的巨噬细胞等肿瘤相关巨噬细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b634/5708216/3a27a7123959/CEJI-42-30879-g001.jpg

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