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The importance of cellular internalization of antibody-targeted carbon nanotubes in the photothermal ablation of breast cancer cells

机译：抗体靶向碳纳米管的细胞内在化在乳腺癌细胞光热消融中的重要性

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Single-walled carbon nanotubes (CNTs) convert absorbed near infrared (NIR) light into heat. The use of CNTs in the NIR-mediated photothermal ablation of tumor cells is attractive because the penetration of NIR light through normal tissues is optimal and the side effects are minimal. Targeted thermal ablation with minimal collateral damage can be achieved by using CNTs attached to tumor-specific monoclonal antibodies (MAbs). However, the role that the cellular internalization of CNTs plays in the subsequent sensitivity of the target cells to NIR-mediated photothermal ablation remains undefined. To address this issue, we used CNTs covalently coupled to an anti-Her2 or a control MAb and tested their ability to bind, internalize, and photothermally ablate Her2~+ but not Her2- breast cancer cell lines. Using flow cytometry, immunofluorescence, and confocal Raman microscopy, we observed the gradual time-dependent receptor-mediated endocytosis of anti-Her2-CNTs whereas a control MAb-CNT conjugate did not bind to the cells. Most importantly, the Her2 ~+ cells that internalized the MAb-CNTs were more sensitive to NIR-mediated photothermal damage than cells that could bind to, but not internalize the MAb-CNTs. These results suggest that both the targeting and internalization of MAb-CNTs might result in the most effective thermal ablation of tumor cells following their exposure to NIR light.
机译：单壁碳纳米管（CNT）将吸收的近红外（NIR）光转换为热量。在NIR介导的肿瘤细胞光热消融中使用CNT是有吸引力的，因为NIR光穿过正常组织的穿透是最佳的，副作用是最小的。通过使用附着于肿瘤特异性单克隆抗体（MAb）的CNT，可以实现具有最小附带损害的靶向热消融。然而，CNTs的细胞内在化在随后靶细胞对NIR介导的光热消融的敏感性中所起的作用仍然不确定。为了解决这个问题，我们使用了与抗Her2或对照MAb共价偶联的CNT，并测试了它们结合，内化和光热消融Her2〜+而不是Her2-乳腺癌细胞系的能力。使用流式细胞仪，免疫荧光和共聚焦拉曼显微术，我们观察到抗Her2-CNTs的时间依赖性受体介导的逐步内吞作用，而对照MAb-CNT共轭物不与细胞结合。最重要的是，内在化MAb-CNT的Her2〜+细胞比能结合但不内化MAb-CNT的细胞对NIR介导的光热损伤更为敏感。这些结果表明，MAb-CNTs的靶向和内在化都可能导致肿瘤细胞在暴露于NIR光后最有效的热消融。

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