Experimental challenges regarding the in vitro investigation of the nanoparticle-biocorona in disease states.

Experimental challenges regarding the in vitro investigation of the nanoparticle-biocorona in disease states.
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DOI:
10.1016/j.tiv.2018.05.003
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发表时间:
2018-09
期刊:
Toxicology in vitro : an international journal published in association with BIBRA
影响因子:
--
通讯作者:
Shannahan J
Shannahan J
中科院分区:
其他
文献类型:
--
作者:
Adamson SX;Lin Z;Chen R;Kobos L;Shannahan J

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由于纳米颗粒的数量和不同的性质,需要利用体外技术对其进行毒理学评价。由于剂量学问题和模拟体内环境的能力,细胞培养系统往往缺乏进行比较毒性评估的能力。在遇到生理环境时,NPs被生物分子包裹,形成生物冕(BC),影响其功能、生物分布和毒性。疾病引起的生物环境改变可以改变BC的形成。本研究评估了低密度脂蛋白(LDL)在改变巨噬细胞对氧化铁(Fe3O4) NPs的反应中的作用。将Fe3O4 NPs在无血清培养基或10%的胎牛血清(含或不含LDL)中孵育形成bc。暴露于标准剂量(25 μg/mL)后,巨噬细胞中Fe3O4 NPs与LDL-BC的关联增强。bc对TNF-α mRNA表达和蛋白水平有不同的诱导作用。所有Fe3O4 NPs暴露后,细胞表面SR-B1表达均降低,而只有LDL-BC NPs增强了线粒体膜电位。这些发现表明LDL的升高可能有助于不同BC的形成,从而影响np -细胞的相互作用和反应。此外,我们的研究强调了在体外评估NP-BC疾病相关变异过程中可能出现的挑战。
Toxicological evaluation of nanoparticles (NPs) requires the utilization of in vitro techniques due to their number and diverse properties. Cell culture systems are often lacking in their ability to perform comparative toxicity assessment due to dosimetry issues and capacity to simulate in vivo environments. Upon encountering a physiological environment, NPs become coated with biomolecules forming a biocorona (BC), influencing function, biodistribution, and toxicity. Disease-induced alterations in the biological milieu can alter BC formation. This study evaluates the role of low-density lipoprotein (LDL) in altering macrophage responses to iron oxide (Fe3O4) NPs. BCs were formed by incubating Fe3O4 NPs in serum-free media, or 10% fetal bovine serum with or without LDL present. Following exposures to a normalized dose (25 μg/mL), macrophage association of Fe3O4 NPs with a LDL-BC was enhanced. TNF-α mRNA expression and protein levels were differentially induced due to BCs. Cell surface expression of SR-B1 was reduced following all Fe3O4 NPs exposures, while only NPs with an LDL-BC enhanced mitochondrial membrane potential. These findings suggest that elevations in LDL may contribute to distinct BC formation thereby influencing NP-cellular interactions and response. Further, our study highlights challenges that may arise during the in vitro evaluation of disease-related variations in the NP-BC.
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