Translocation of Functionalized Multi-Walled Carbon Nanotubes across Human Pulmonary Alveolar Epithelium: Dominant Role of Epithelial Type 1 Cells.

Translocation of Functionalized Multi-Walled Carbon Nanotubes across Human Pulmonary Alveolar Epithelium: Dominant Role of Epithelial Type 1 Cells.
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DOI:
10.1021/acsnano.5b08218
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发表时间:
2016-05-24
期刊:
影响因子:
17.1
通讯作者:
Porter AE
Porter AE
中科院分区:
材料科学1区
文献类型:
--
作者:
Ruenraroengsak P;Chen S;Hu S;Melbourne J;Sweeney S;Thorley AJ;Skepper JN;Shaffer MS;Tetley TD;Porter AE

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短功能化多壁碳纳米管(short-fMWCNTs)通过肺呼吸上皮屏障的摄取和转运取决于理化性质和细胞类型。采用定量成像和光谱技术,研究了肺泡上皮屏障的两种单一培养模型,永生化的人肺泡上皮1型(TT 1)细胞和原代人肺泡上皮2型(AT 2)细胞对长度为300和700 nm的聚(4-乙烯基吡啶)功能化多壁碳纳米管(p(4VP)-MWCNTs)的摄取和转运。p(4VP)-MWCNT对TT 1和AT 2细胞没有毒性,但显著降低了屏障完整性(*p<0.01)。在70%的TT 1细胞中观察到p(4VP)-MWCNT摄取,这与屏障完整性受损和基底外侧p(4VP)-MWCNT易位相关。TT 1细胞对300 nm p(4VP)-MWCNTs的摄取量较小,但显著高于700 nm p(4VP)-MWCNTs。高达3%的300和700 nm p(4VP)-MWCNT到达基底室;这种相对较低的量出现是因为支持transwell膜使易位到基底室的p(4VP)-MWCNT的量最小化,可见被困在基底外侧细胞膜和膜之间。仅8%的AT 2细胞内化p(4VP)-MWCNT,占应用的p(4VP)-MWCNT的17%,对屏障功能有短暂影响,最初下降,然后恢复正常;没有MWCNT基底外侧易位。转运速率是MWCNT长度调节的。AT 2细胞对p(4VP)-MWCNT的摄取相对较低,这反映了2型细胞分泌物的主要屏障作用以及1型和2型肺泡上皮细胞之间的功能差异。
Uptake and translocation of short functionalised multi-walled carbon nanotubes (short-fMWCNTs) through the pulmonary respiratory epithelial barrier depend on physicochemical property and cell type. Two mono-culture models, immortalised human alveolar epithelial type 1 (TT1) cells and primary human alveolar epithelial type 2 cells (AT2), which constitute the alveolar epithelial barrier, were employed to investigate the uptake and transport of 300 and 700nm in length, poly(4-vinyl pyridine)-functionalized, multi-walled carbon nanotubes (p(4VP)-MWCNTs) using quantitative imaging and spectroscopy techniques. The p(4VP)-MWCNT exhibited no toxicity on TT1 and AT2 cells, but significantly decreased barrier integrity (*p<0.01). Uptake of p(4VP)-MWCNTs was observed in 70% of TT1 cells, correlating with compromised barrier integrity and basolateral p(4VP)-MWCNT translocation. There was a small but significantly greater uptake of 300nm p(4VP)-MWCNTs than 700nm p(4VP)-MWCNTs by TT1 cells. Up to 3% of both the 300 and 700nm p(4VP)-MWCNTs reach the basal chamber; this relatively low amount arose because the supporting transwell membrane minimized the amount of p(4VP)-MWCNT translocating to the basal chamber, seen trapped between the basolateral cell membrane and the membrane. Only 8% of AT2 cells internalised p(4VP)-MWCNT, accounting for 17% of applied p(4VP)-MWCNT), with transient effects on barrier function, which initially fell then returned to normal; there was no MWCNT basolateral translocation. The transport rate was MWCNT-length-modulated. The comparatively lower p(4VP)-MWCNT uptake by AT2 cells is proposed to reflect a primary barrier effect of type 2 cell secretions and the functional differences between the type 1 and type 2 alveolar epithelial cells.
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