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金刚石纳米颗粒对血管内皮细胞的细胞类型特异性毒性的差异取决于细胞暴露于纳米颗粒的情况。

Differences in the Cell Type-Specific Toxicity of Diamond Nanoparticles to Endothelial Cells Depending on the Exposure of the Cells to Nanoparticles.

机构信息

Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, 02-786, Poland.

Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, 00-654, Poland.

出版信息

Int J Nanomedicine. 2023 May 29;18:2821-2838. doi: 10.2147/IJN.S411424. eCollection 2023.

Abstract

INTRODUCTION

Diamond nanoparticles are considered to be one of the most cytocompatible carbon nanomaterials; however, their toxicity varies significantly depending on the analysed cell types. The aim was to investigate the specific sensitivity of endothelial cells to diamond nanoparticles dependent on exposure to nanoparticles.

METHODS

Diamond nanoparticles were characterized with Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS). Toxicity of diamond nanoparticles was assessed for endothelial cells (HUVEC), human mammary epithelial cells (HMEC) and HS-5 cell line. The effect of diamond nanoparticles on the level of ROS, NO, NADPH and protein synthesis of angiogenesis-related proteins of endothelial cells was evaluated.

RESULTS AND DISCUSSION

Our studies demonstrated severe cell type-specific toxicity of diamond nanoparticles to endothelial cells (HUVEC) depending on nanoparticle surface interaction with cells. Furthermore, we have assessed the effect on cytotoxicity of the bioconjugation of nanoparticles with a peptide containing the RGD motive and a serum protein corona. Our study suggests that the mechanical interaction of diamond nanoparticles with the endothelial cell membranes and the endocytosis of nanoparticles lead to the depletion of NADPH, resulting in an intensive synthesis of ROS and a decrease in the availability of NO. This leads to severe endothelial toxicity and a change in the protein profile, with changes in major angiogenesis-related proteins, including VEGF, bFGF, ANPT2/TIE-2, and MMP, and the production of stress-related proteins, such as IL-6 and IL-8.

CONCLUSION

We confirmed the presence of a relationship between the toxicity of diamond nanoparticles and the level of cell exposure to nanoparticles and the nanoparticle surface. The results of the study give new insights into the conditioned toxicity of nanomaterials and their use in biomedical applications.

摘要

简介

金刚石纳米颗粒被认为是最具细胞相容性的碳纳米材料之一;然而,它们的毒性因所分析的细胞类型而异。本研究旨在探讨内皮细胞对金刚石纳米颗粒的敏感性取决于暴露于纳米颗粒的具体情况。

方法

采用拉曼光谱、傅里叶变换红外光谱(FTIR)和动态光散射(DLS)对金刚石纳米颗粒进行了表征。评估了金刚石纳米颗粒对内皮细胞(HUVEC)、人乳腺上皮细胞(HMEC)和 HS-5 细胞系的毒性。评估了金刚石纳米颗粒对内皮细胞相关蛋白的 ROS、NO、NADPH 和蛋白质合成水平的影响。

结果与讨论

我们的研究表明,金刚石纳米颗粒对内皮细胞(HUVEC)的细胞类型特异性毒性取决于纳米颗粒与细胞的表面相互作用。此外,我们还评估了纳米颗粒与含有 RGD 基序的肽和血清蛋白冠的生物缀合对细胞毒性的影响。我们的研究表明,金刚石纳米颗粒与内皮细胞膜的机械相互作用和纳米颗粒的内吞作用导致 NADPH 耗竭,从而导致 ROS 的大量合成和 NO 的可用性降低。这导致严重的内皮细胞毒性和蛋白质谱的变化,主要涉及血管生成相关蛋白,包括 VEGF、bFGF、ANPT2/TIE-2 和 MMP,以及应激相关蛋白,如 IL-6 和 IL-8。

结论

我们证实了金刚石纳米颗粒的毒性与细胞暴露于纳米颗粒的程度和纳米颗粒表面之间存在关系。研究结果为纳米材料的条件毒性及其在生物医学应用中的应用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/10237202/08017b9b117c/IJN-18-2821-g0001.jpg

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