The impact of subcellular location on the near infrared-mediated thermal ablation of cells by targeted carbon nanotubes.
The impact of subcellular location on the near infrared-mediated thermal ablation of cells by targeted carbon nanotubes.
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DOI：
10.1088/0957-4484/27/42/425102
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发表时间：
2016-10-21
期刊：
影响因子：
3.5
通讯作者：
Draper RK
中科院分区：
文献类型：
--
作者：
Murali VS;Wang R;Mikoryak CA;Pantano P;Draper RK
单壁碳纳米管（SWNTs）被用于近红外（NIR）介导的肿瘤细胞热消融，因为它们有效地将吸收的近红外光转化为热量。尽管单壁碳纳米管具有治疗潜力，但目前还没有发表的研究直接量化一个细胞需要多少单壁碳纳米管才能达到预期的杀伤效率，或者单壁碳纳米管杀死细胞的最有效亚细胞位置是什么。在这里，我们测量了杀伤效率的剂量反应曲线，该曲线与叶酸靶向swnt的测量量相关，这些swnt要么位于正常大鼠肾（NRK）细胞表面，要么位于空泡室内。将培养基中不同浓度的swnt与细胞在4°C下孵育30分钟后，测量细胞表面的叶酸靶向swnt。将细胞与不同浓度的单壁碳纳米管在37℃培养液中孵育6小时后，测量液泡室中叶酸靶向单壁碳纳米管的含量。在近红外光照射的标准条件下，观察到~13 pg/ cells的SWNT负载足以杀死90%的细胞。在相同的近红外照射条件下，当~3.5 pg/细胞的单壁碳纳米管内化于内体/溶酶体腔室时，约50%的细胞被杀死，而当~3.5 pg/细胞的单壁碳纳米管内化于细胞表面时，约5%的细胞被杀死。通过将SWNT的拉曼成像与已知亚细胞标记物的荧光图像合并，验证了SWNT的亚细胞位置。据我们所知，这是第一次将已知亚细胞位置的SWNT数量与热消融的剂量标准化效果联系起来，结果支持这样的观点，即局限于质膜的SWNT在nir介导的细胞杀伤中不如内化在内体/溶酶体囊泡中的等量SWNT有效。
Single-walled carbon nanotubes (SWNTs) are used in the near infrared (NIR)-mediated thermal ablation of tumor cells because they efficiently convert absorbed NIR light into heat. Despite the therapeutic potential of SWNTs, there have been no published studies that directly quantify how many SWNTs need be associated with a cell to achieve a desired efficiency of killing, or what is the most efficient subcellular location of SWNTs for killing cells. Herein we measured dose response curves for the efficiency of killing correlated to the measured amounts of folate-targeted SWNTs that were either on the surface or within the vacuolar compartment of normal rat kidney (NRK) cells. Folate-targeted SWNTs on the cell surface were measured after different concentrations of SWNTs in medium were incubated with cells for 30 min at 4 °C. Folate-targeted SWNTs within the vacuolar compartments were measured after cells were incubated with different concentrations of SWNTs in medium for 6 h at 37 °C. It was observed that a SWNT load of ~13 pg/cell when internalized was sufficient to kill 90% of the cells under standard conditions of NIR light irradiation. When ~3.5 pg/cell of SWNTs were internalized within the endosomal/lysosomal compartments, ~50% of the cells were killed, but when ~3.5 pg/cell of SWNTs were confined to the cell surface only ~5% of the cells were killed under the same NIR irradiation condition. The SWNT subcellular locations were verified using Raman imaging of SWNTs merged with fluorescence images of known subcellular markers. To our knowledge, this is the first time that SWNT amounts at known subcellular locations have been correlated with a dose-normalized efficacy of thermal ablation and the results support the idea that SWNTs confined to the plasma membrane are not as effective in NIR-mediated cell killing as an equivalent amount of SWNTs when internalized within the endosomal/lysosomal vesicles.
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