细胞年龄对纳米颗粒吸收和毒性的影响：在纳米生物界面被忽视的因素。,ACS Applied Materials & Interfaces

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细胞年龄对纳米颗粒吸收和毒性的影响：在纳米生物界面被忽视的因素。
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-10-21 , DOI: 10.1021/acsami.9b15533
Parisa Foroozandeh ₁ , Azlan Abdul Aziz _{1,

2} , Morteza Mahmoudi ₃

Affiliation

纳米技术的临床翻译取得的成功有限，至少部分是由于在纳米系统的性质（例如，纳米粒子的理化性质），纳米生物界面（例如，蛋白质电晕组成）和细胞特性方面存在一些被忽视的因素（例如，单元格类型）。在过去的十年中，一些被忽略的因素包括个性化和疾病特异性蛋白电晕（纳米粒子进入生物流体后在纳米颗粒表面形成的生物分子层），温育温度，局部温度梯度，细胞形状和细胞性别。被介绍。在这里，我们假设并验证了细胞年龄是纳米医学领域另一个被忽视的因素。为了验证我们的假设，模型的纳米颗粒的细胞毒性和摄取情况（即，在年轻和衰老的细胞（即来自人胎肺的IMR90成纤维细胞和来自人胎结肠的CCD841CoN上皮细胞）中探查了PEG化的量子点（QD），结果表明细胞-纳米颗粒相互作用与细胞年龄之间存在显着相关性。例如，观察到聚乙二醇化的量子点对衰老的IMR90和CCD841CoN细胞具有急性毒性，导致溶酶体膜通透化，从而引起细胞坏死。相反，年轻细胞对相同数量的QD和相同的孵育时间具有弹性。还发现蛋白质电晕的形成可以延迟量子点对衰老细胞的毒性。这些发现表明，细胞衰老过程具有引起细胞器和正常功能恶化的能力。这项研究的结果表明概念的证明，即细胞年龄可能在生物系统对纳米粒子技术的反应中起关键作用。因此，应仔细考虑细胞年龄对纳米生物相互作用的影响，并且有关细胞年龄的信息（例如，传代数和细胞供体的年龄）应包括在纳米医学论文中，以促进纳米技术的临床翻译并帮助科学家以更好地设计和生产安全有效的针对年龄的特定诊断/治疗纳米粒子。

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Effect of Cell Age on Uptake and Toxicity of Nanoparticles: The Overlooked Factor at the Nanobio Interface

Clinical translation of nanotechnologies has limited success, at least in part, due to the existence of several overlooked factors on the nature of the nanosystem (e.g., physicochemical properties of nanoparticles), nanobio interfaces (e.g., protein corona composition), and the cellular characteristics (e.g., cell type). In the past decade, several ignored factors including personalized and disease-specific protein corona (a layer of formed biomolecules at the surface of nanoparticles upon their entrance into a biological fluid), incubating temperature, local temperature gradient, cell shape, and cell sex has been introduced. Here, it was hypothesized and validated cell age as another overlooked factor in the field of nanomedicine. To test our hypothesis, cellular toxicity and uptake profiles of our model nanoparticles (i.e., PEGylated quantum dots, QDs) were probed in young and senescent cells (i.e., IMR90 fibroblast cells from human fetal lung and CCD841CoN epithelial cells from human fetal colon) and the outcomes revealed substantial dependency of cell-nanoparticles interactions to the cell age. For example, it was observed that the PEGylated QDs were acutely toxic to senescent IMR90 and CCD841CoN cells, leading to lysosomal membrane permeabilization which caused cell necrosis; in contrast, the young cells were resilient to the exact same amount of QDs and the same incubation time. It was also found that the formation of protein corona could delay the QDs’ toxicity on senescent cells. These findings suggest that the cellular aging process have a capacity to cause deteriorative effects on their organelles and normal functions. The outcomes of this study suggest the proof-of-concept that cell age may have critical role in biosystem responses to nanoparticle technologies. Therefore, the effect of cell age should be carefully considered on the nanobio interactions and the information about cellular age (e.g., passage number and age of the cell donor) should be included in the nanomedicine papers to facilitate clinical translation of nanotechnologies and to help scientists to better design and produce safe and efficient diagnostic/therapeutic age-specific nanoparticles.

更新日期：2019-10-21

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