The importance of cellular internalization of antibody-targeted carbon nanotubes in the photothermal ablation of breast cancer cells
The importance of cellular internalization of antibody-targeted carbon nanotubes in the photothermal ablation of breast cancer cells
复制标题
DOI：
10.1088/0957-4484/22/9/095101
复制
发表时间：
2011-03-04
期刊：
影响因子：
3.5
通讯作者：
Vitetta, Ellen S.
中科院分区：
文献类型：
--
作者：
Marches, Radu;Mikoryak, Carole;Vitetta, Ellen S.
单壁碳纳米管 (CNT) 将吸收的近红外 (NIR) 光转化为热量。在近红外介导的肿瘤细胞光热消融中使用碳纳米管很有吸引力，因为近红外光对正常组织的穿透力是最佳的，而且副作用最小。通过使用附着在肿瘤特异性单克隆抗体 (MAb) 上的碳纳米管，可以实现附带损伤最小的靶向热消融。然而，碳纳米管的细胞内化在靶细胞随后对近红外介导的光热消融的敏感性中所起的作用仍不清楚。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、内在化和光热消融 Her2(+) 但不是 Her2(-) 乳腺癌细胞系的能力。使用流式细胞术、免疫荧光和共焦拉曼显微镜，我们观察到抗 Her2-CNT 逐渐依赖于时间依赖性受体介导的内吞作用，而对照 MAb-CNT 缀合物不与细胞结合。最重要的是，内化 MAb-CNT 的 Her2(+) 细胞比能够结合但不内化 MAb-CNT 的细胞对 NIR 介导的光热损伤更敏感。这些结果表明，MAb-CNT 的靶向和内化可能会导致肿瘤细胞在暴露于近红外光后最有效的热消融。
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.