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Integrated molecular targeting of IGF1R and HER2 surface receptors and destruction of breast cancer cells using single wall carbon nanotubes

机译:使用单壁碳纳米管对IGF1R和HER2表面受体进行分子靶向整合并破坏乳腺癌细胞

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Molecular targeting and photodynamic therapy have shown great potential for selective cancer therapy. We hypothesized that monoclonal antibodies that are specific to the IGF1 receptor and HER2 cell surface antigens could be bound to single wall carbon nanotubes (SWCNT) in order to concentrate SWCNT on breast cancer cells for specific near-infrared phototherapy. SWCNT functionalized with HER2 and IGF1R specific antibodies showed selective attachment to breast cancer cells compared to SWCNT functionalized with non-specific antibodies. After the complexes were attached to specific cancer cells, SWCNT were excited by similar to 808 nm infrared photons at similar to 800 mW cm(-2) for 3 min. Viability after phototherapy was determined by Trypan blue exclusion. Cells incubated with SWCNTon-specific antibody hybrids were still alive after photo-thermal treatment due to the lack of SWNT binding to the cell membrane. All cancerous cells treated with IGF1R and HER2 specific antibody/SWCNT hybrids and receiving infrared photons showed cell death after the laser excitation. Quantitative analysis demonstrated that all the cells treated with SWCNT/IGF1R and HER2 specific antibody complex were completely destroyed, while more than 80+ACU- of the cells with SWCNTon-specific antibody hybrids remained alive. Following multi-component targeting of IGF1R and HER2 surface receptors, integrated photo-thermal therapy in breast cancer cells led to the complete destruction of cancer cells. Functionalizing SWCNT with antibodies in combination with their intrinsic optical properties can therefore lead to a new class of molecular delivery and cancer therapeutic systems.
机译:分子靶向和光动力疗法已显示出选择性癌症疗法的巨大潜力。我们假设对IGF1受体和HER2细胞表面抗原具有特异性的单克隆抗体可以与单壁碳纳米管(SWCNT)结合,以便将SWCNT集中在乳腺癌细胞上用于特定的近红外光疗。与用非特异性抗体功能化的SWCNT相比,用HER2和IGF1R特异性抗体功能化的SWCNT显示出对乳腺癌细胞的选择性附着。将复合物附着到特定癌细胞后,SWCNT被类似于808 nm的红外光子以类似的800 mW cm(-2)激发3分钟。通过台盼蓝排除法测定光疗后的生存力。与SWCNT /非特异性抗体杂交体一起孵育的细胞由于缺乏与细胞膜结合的SWNT而在光热处理后仍然存活。用IGF1R和HER2特异性抗体/ SWCNT杂种处理并接受红外光子的所有癌细胞在激光激发后均显示细胞死亡。定量分析表明,用SWCNT / IGF1R和HER2特异性抗体复合物处理的所有细胞均被完全破坏,而超过80 + ACU-的SWCNT /非特异性抗体杂种细胞仍然存活。在对IGF1R和HER2表面受体进行多组分靶向后,乳腺癌细胞中的综合光热疗法导致癌细胞的完全破坏。因此,结合抗体的内在光学特性将SWCNT功能化可以导致一类新的分子递送和癌症治疗系统。

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