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首页> 外文期刊>RSC Advances >Implications for blood-brain-barrier permeability, in vitro oxidative stress and neurotoxicity potential induced by mesoporous silica nanoparticles: effects of surface modification
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Implications for blood-brain-barrier permeability, in vitro oxidative stress and neurotoxicity potential induced by mesoporous silica nanoparticles: effects of surface modification

机译：血脑阻隔渗透性的影响，体外氧化应激和介孔二氧化硅纳米粒子诱导的神经毒性潜力：表面改性的作用

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摘要

The increase in the abundance and practical applications of nanomaterials has led to growing concern over the potential adverse effects of nanoparticles on human health. Their unique structure makes mesoporous silica nanoparticles (MSNs) an ideal platform for developing multifunctional nanocarriers, including non-viral gene delivery in the central nervous system (CNS). However, the potential neurotoxicity of the MSNs remains largely unclear. In this study, we explored the biological effect of MCM-41 type MSNs on blood-brain-barrier (BBB) permeability, neuronal damage, and the mediation of neurotoxicity with surface chemistry. With or without the ligand transferrin (Tf), which could interact with the transferrin receptor expressed at the BBB, in vivo imaging indicated that both MSN-Cy-Tf and MSN-Cy may enter into the brain, suggesting their potential to deliver therapeutic agents across the BBB. However, a risk arises that is associated with this permeability. A histological observation of the hippocampus confirms the CNS delivery of MSNs and indicates neuronal damage, characterized by neuronal cell loss, nuclei shrinkage, and the disintegration of neurons, suggestive of in vivo neurotoxicity. With the PC12 cell, a model for the dopaminergic neuron, an in vitro examination suggests that various surface modified MSNs decrease the cell viability and cause oxidative stress with an elevation of reactive oxygen species (ROS), a depletion of glutathione (GSH), leakage of lactate dehydrogenase (LDH), and the generation of malondialdehyde (MDA) in a concentration-dependent manner. Compared with the pristine MSNs which induce the severest injury impact on the cells, thiol modified MSN-SH nanoparticles show significantly lower injury effects among the test MSNs, suggesting the possibility to mediate the neurotoxicity by modifying the surface chemistry of this kind of the nanomaterial for biomedical applications.
机译：纳米材料的丰度和实际应用的增加导致对纳米颗粒对人体健康的潜在不利影响的影响。它们独特的结构使得介孔二氧化硅纳米粒子（MSNS）成为开发多功能纳米载体的理想平台，包括中枢神经系统（CNS）中的非病毒基因递送。然而，MSNS的潜在神经毒性仍然很大程度上不清楚。在这项研究中，我们探讨了MCM-41型MSN的生物学效应对血脑屏障（BBB）渗透性，神经元损伤以及具有表面化学神经毒性的调解。有或没有配体转移素（TF），其可以与BBB在BBB表达的转移素受体相互作用，表明MSN-CY-TF和MSN-CY可以进入大脑，表明它们递送治疗剂的可能性跨越BBB。然而，出现了与这种渗透性相关的风险。海马的组织学观察证实了MSN的CNS递送，表明神经元损伤，其特征在于神经元细胞损失，核收缩和神经元的崩解，暗示体内神经毒性。通过PC12细胞，一种用于多巴胺能神经元的模型，体外检查表明各种表面改性MSN减少了细胞活力并导致氧化应激与反应性氧物种（ROS）的升高，谷胱甘肽（GSH）的耗尽，泄漏乳酸脱氢酶（LDH），以及以浓度依赖性方式产生丙二醛（MDA）。与诱导对细胞最严重的损伤影响的原始MSN，硫醇改性MSN-SH纳米粒子显示出测试MSN的损伤显着较低，表明通过改变这种纳米材料的表面化学来介导神经毒性的可能性生物医学应用。

著录项

  • 来源
    《RSC Advances》 |2016年第4期|共10页
  • 作者

    Zhou Ming; Xie Linlin; Fang Chen-Jie; Yang Hua; Wang Yan-Jie; Zhen Xiao-Yu; Yan Chun-Hua; Wang Yuji; Zhao Ming; Peng Shiqi;

  • 作者单位

    Capital Med Univ Beijing Area Major Lab Peptide &

    Small Mol Drugs Res Ctr Endogenous Prophylact Minist Educ China Beijing Lab Biomed Mat Coll Pharmaceut Sci Beijing 100069 Peoples R China;

    Capital Med Univ Beijing Area Major Lab Peptide &

    Small Mol Drugs Res Ctr Endogenous Prophylact Minist Educ China Beijing Lab Biomed Mat Coll Pharmaceut Sci Beijing 100069 Peoples R China;

    Capital Med Univ Beijing Area Major Lab Peptide &

    Small Mol Drugs Res Ctr Endogenous Prophylact Minist Educ China Beijing Lab Biomed Mat Coll Pharmaceut Sci Beijing 100069 Peoples R China;

    Capital Med Univ Med Expt &

    Test Ctr Beijing 100069 Peoples R China;

    Peking Univ Beijing Natl Lab Mol Sci State Key Lab Rare Earth Mat Chem &

    Applicat PKU HKU Joint Lab Rare Earth Mat &

    Bioinorgan Che Beijing 100871 Peoples R China;

    Peking Univ Beijing Natl Lab Mol Sci State Key Lab Rare Earth Mat Chem &

    Applicat PKU HKU Joint Lab Rare Earth Mat &

    Bioinorgan Che Beijing 100871 Peoples R China;

    Peking Univ Beijing Natl Lab Mol Sci State Key Lab Rare Earth Mat Chem &

    Applicat PKU HKU Joint Lab Rare Earth Mat &

    Bioinorgan Che Beijing 100871 Peoples R China;

    Capital Med Univ Beijing Area Major Lab Peptide &

    Small Mol Drugs Res Ctr Endogenous Prophylact Minist Educ China Beijing Lab Biomed Mat Coll Pharmaceut Sci Beijing 100069 Peoples R China;

    Capital Med Univ Beijing Area Major Lab Peptide &

    Small Mol Drugs Res Ctr Endogenous Prophylact Minist Educ China Beijing Lab Biomed Mat Coll Pharmaceut Sci Beijing 100069 Peoples R China;

    Capital Med Univ Beijing Area Major Lab Peptide &

    Small Mol Drugs Res Ctr Endogenous Prophylact Minist Educ China Beijing Lab Biomed Mat Coll Pharmaceut Sci Beijing 100069 Peoples R China;

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