The unique properties of single walled carbon nanotubes (SWCNTs) make them viable candidates for versatile implementation in the next generation of biomedical devices for targeted delivery of chemotherapeutic agents or cellular-sensing probes. Such implementation requires user-tailored changes in SWCNT's physicochemical characteristics to allow for efficient cellular integration while maintaining nanotubes' functionality. However, isolated reports showed that user-tailoring could induce deleterious effects in exposed cells, from decrease in cellular proliferation, to changes in cellular adhesion, generation of reactive oxygen species or phenotypical variations, just to name a few. Before full implementation of SWCNTs is achieved, their toxicological profiles need to be mechanistically correlated with their physicochemical properties to determine how the induced cellular fate is related to the exposure conditions or samples' characteristics. Our study provides a comprehensive analysis of the synergistic cyto- and genotoxic effects resulted from short-term exposure of human lung epithelial cells to pristine (as manufactured) and user-tailored SWCNTs, as a function of their physicochemical properties. Specifically, through a systematic approach we are correlating the nanotube uptake and nanotube-induced cellular changes to the sample's physicochemical characteristics (e.g., metal impurities, length, agglomerate size, surface area, dispersion, and surface functionalization). By identifying changes in active hallmarks involved in cell-cell connections and maintaining epithelial layer integrity, we also determine the role that short-term exposure to SWCNTs plays in the overall cellular fate and cellular transformation. Lastly, we assess cellular structure-function relationships to identify non-apoptotic pathways induced by SWCNTs exposure that could however lead to changes in cellular behavior and cellular transformation. Our results show that the degree of cell transformation is a function of the physicochemical properties of the SWCNT, with the nanotube with higher length, higher metal content and larger agglomerate size reducing cell viability to a larger extent. Such changes in cell viability are also complemented by changes in cell structure, cycle and cell-cell interactions, all responsible for maintaining cell fate.

中文翻译：

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碳纳米管物理化学性质影响整体细胞行为和命运

单壁碳纳米管 (SWCNT) 的独特特性使其成为下一代生物医学设备中多功能实施的可行候选者，用于靶向递送化学治疗剂或细胞传感探针。这种实现需要用户定制的 SWCNT 物理化学特性的变化，以允许有效的细胞整合，同时保持纳米管的功能。然而，孤立的报告表明，用户定制可能会对暴露的细胞产生有害影响，从细胞增殖的减少到细胞粘附的变化、活性氧的产生或表型变异，仅举几例。在实现 SWCNT 的全面实施之前，它们的毒理学特征需要与它们的理化特性机械相关，以确定诱导的细胞命运如何与暴露条件或样品特征相关。我们的研究提供了对人类肺上皮细胞短期暴露于原始（制造的）和用户定制的 SWCNT 所产生的协同细胞和基因毒性作用的综合分析，作为其理化特性的函数。具体而言，我们通过系统方法将纳米管吸收和纳米管诱导的细胞变化与样品的物理化学特性（例如，金属杂质、长度、团聚体尺寸、表面积、分散和表面功能化）相关联。通过识别涉及细胞-细胞连接和维持上皮层完整性的活性标志的变化，我们还确定了短期暴露于 SWCNT 在整体细胞命运和细胞转化中的作用。最后，我们评估细胞结构-功能关系，以确定由 SWCNTs 暴露诱导的非凋亡途径，但可能导致细胞行为和细胞转化的变化。我们的结果表明，细胞转化的程度是 SWCNT 理化性质的函数，具有更长长度、更高金属含量和更大团聚体尺寸的纳米管在更大程度上降低了细胞活力。细胞活力的这种变化也得到细胞结构、周期和细胞间相互作用变化的补充，