Aggregation Reduces Subcellular Localization and Cytotoxicity of Single-Walled Carbon Nanotubes
Aggregation Reduces Subcellular Localization and Cytotoxicity of Single-Walled Carbon Nanotubes
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DOI：
10.1021/acsami.2c02238
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发表时间：
2022-05-04
影响因子：
9.5
通讯作者：
Roxbury, Daniel
中科院分区：
文献类型：
--
作者：
Gravely, Mitchell;Kindopp, Aidan;Roxbury, Daniel
由于具有许多理想的光学特性，荧光单壁碳纳米管（SWCNTs）的非共价生物分子功能化导致了许多体外和体内传感和成像应用。在这些应用中，通常假定原始的、单分散的SWCNTs通过所谓的纳米生物界面（例如细胞膜）与活细胞相互作用并进入活细胞。尽管有许多关于这一假设的基础研究发表，但众所周知，纳米材料在接触纳米生物界面之前，有在含有蛋白质的环境中聚集的倾向。在这里，我们使用具有特定聚集度的dna功能化SWCNTs以及近红外高光谱显微镜和毒理学分析，发现尽管内化率相同，但最初聚集的SWCNTs不会在单个亚细胞位置进一步积累。除了亚细胞积聚外，在各种长期细胞毒性和实时增殖试验中，最初聚集程度较低的SWCNTs可诱导显著的有害影响，这与最初聚集程度较低的SWCNTs相比有明显不同。这些发现表明，聚集状态是与工程纳米材料的细胞内加工和毒理学反应相关的关键组成部分。
The non-covalent biomolecular functionalization of fluorescent single-walled carbon nanotubes (SWCNTs) has resulted in numerous in vitro and in vivo sensing and imaging applications due to many desirable optical properties. In these applications, it is generally presumed that pristine, singly dispersed SWCNTs interact with and enter live cells at the so-called nanobiointerface, for example, the cell membrane. Despite numerous fundamental studies published on this presumption, it is known that nanomaterials have the propensity to aggregate in proteincontaining environments before ever contacting the nano-biointerface. Here, using DNA-functionalized SWCNTs with defined degrees of aggregation as well as near-infrared hyperspectral microscopy and toxicological assays, we show that despite equal rates of internalization, initially aggregated SWCNTs do not further accumulate within individual subcellular locations. In addition to subcellular accumulations, SWCNTs initially with a low degree of aggregation can induce significant deleterious effects in various long-term cytotoxicity and real-time proliferation assays, which are markedly different when compared to those of SWCNTs that are initially aggregated. These findings suggest the importance of the aggregation state as a critical component related to intracellular processing and toxicological response of engineered nanomaterials.