Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery.
Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery.
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DOI：
10.1021/nn800551s
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发表时间：
2009-02-24
期刊：
影响因子：
17.1
通讯作者：
Rusling, James F.
中科院分区：
文献类型：
--
作者：
Bhirde, Ashwin A.;Patel, Vyomesh;Gavard, Julie;Zhang, Guofeng;Sousa, Alioscka A.;Masedunskas, Andrius;Leapman, Richard D.;Weigert, Roberto;Gutkind, J. Silvio;Rusling, James F.
关键词：
基于碳纳米管的药物输送在癌症治疗中具有很大的前景。在这里，我们报道了第一个使用药物-单壁碳纳米管（SWNT）生物偶联物在体内靶向杀死癌细胞，并证明其疗效优于非靶向生物偶联物。将一线抗癌药物顺铂和表皮生长因子（EGF）附着在swnt上特异性靶向鳞癌，非靶向对照为不含EGF的swnt -顺铂。使用Qdot发光和共聚焦显微镜对过表达EGF受体（EGFR）的头颈部鳞癌细胞（HNSCC）进行的初步体外成像研究显示，SWNT-Qdot-EGF生物偶联物迅速内化到癌细胞中。没有EGF的对照细胞摄取有限，癌细胞中EGFR的siRNA敲低阻断了摄取，揭示了EGFR结合的重要性。活体三色双光子活体视频成像显示，注射到活小鼠体内的SWNT-Qdot-EGF被HNSCC肿瘤选择性摄取，而未注射EGF的SWNT-Qdot对照则在<20分钟内被肿瘤区域清除。用swnt -顺铂- egf处理的HNSCC细胞也被选择性杀死，而不具有EGF-EGFR结合特征的对照系统不影响细胞增殖。最重要的是，与非靶向swnt -顺铂相比，靶向swnt -顺铂- egf治疗的小鼠肿瘤生长的消退速度更快。
Carbon nanotube-based drug delivery holds great promise for cancer therapy. Herein we report the first targeted, in vivo killing of cancer cells using a drug-single wall carbon nanotube (SWNT) bioconjugate, and demonstrate efficacy superior to non-targeted bioconjugates. First line anti-cancer agent cisplatin and epidermal growth factor (EGF) were attached to SWNTs to specifically target squamous cancer, and the non-targeted control was SWNT-cisplatin without EGF. Initialin vitro imaging studies with head and neck squamous carcinoma cells (HNSCC) overexpressing EGF receptors (EGFR) using Qdot luminescence and confocal microscopy showed that SWNT-Qdot-EGF bioconjugates internalized rapidly into the cancer cells. Limited uptake occurred for control cells without EGF, and uptake was blocked by siRNA knockdown of EGFR in cancer cells, revealing the importance of EGFEGFR binding. Three color, two-photon intra-vital video imagingin vivo showed that SWNT-Qdot-EGF injected into live mice was selectively taken up by HNSCC tumors, but SWNT-Qdot controls with no EGF were cleared from the tumor region in <20 min. HNSCC cells treated with SWNT-cisplatin-EGF were also killed selectively, while control systems that did not feature EGF-EGFR binding did not influence cell proliferation. Most significantly, regression of tumor growth was rapid in mice treated with targeted SWNT-cisplatin-EGF relative to non-targeted SWNT-cisplatin.
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