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载有抗 EGFR 抗体的银纳米颗粒使鼻咽癌细胞对放疗敏感。

Silver nanoparticles coupled to anti‑EGFR antibodies sensitize nasopharyngeal carcinoma cells to irradiation.

机构信息

Jiangsu Collaborative Innovation Center of Tumor Prevention and Treatment by Traditional Chinese Medicine (TCM), Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.

Department of Clinical Laboratory, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

出版信息

Mol Med Rep. 2017 Dec;16(6):9005-9010. doi: 10.3892/mmr.2017.7704. Epub 2017 Oct 4.

Abstract

Radiotherapy is the major form of treatment for head and neck carcinoma, a malignant tumour of epithelial origin. The identification of agents, which can be co‑administered in order to sensitize these tumours to radiotherapy, has become a major focus of investigations. In the present study, a novel 20 nm nanocomposite, Ag/C225, was constructed, which consisted of silver nanoparticles (AgNPs) conjugated to an epidermal growth factor receptor‑specific antibody (C225). Physical characterization demonstrated that the Ag/C225 nanoparticles were spherical and dispersed well in water. Enzyme‑linked immunosorbent assays showed that the activity of C225 was preserved in the Ag/C225 nanoparticles. The results of 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide analysis revealed that AgNPs and Ag/C225 inhibited the proliferation of nasopharyngeal carcinoma epithelial (CNE) cells in a dose‑ and time‑dependent manner. Flow cytometry revealed that AgNPs and Ag/C225 induced the apoptosis of CNEs, and abrogated G2 arrest; the latter effect was more marked with Ag/C225 than with AgNPs. Clonogenic assays indicated that AgNPs and Ag/C225 increased the sensitivity of CNEs to irradiation. The sensitizer enhancement ratios were 1.610±0.012 and 1.405±0.033 Gy for AgNPs and Ag/C225, respectively. Western blot analysis revealed that combining X‑ray irradiation with either AgNPs or Ag/C225 reduced the expression levels of DNA damage/repair proteins Ku‑70, Ku‑80 and Rad51; Ag/C225 was also more effective than AgNPs in this context. These results indicated that AgNPs and Ag/C225 effectively enhanced CNE cell radiosensitivity in vitro. Therefore, these potent agents may be considered for use as radiosensitizers during the treatment of human nasopharyngeal carcinoma.

摘要

放射疗法是头颈部癌(一种上皮来源的恶性肿瘤)的主要治疗形式。鉴定可以联合使用以增强这些肿瘤对放射疗法敏感性的试剂已成为研究的主要重点。在本研究中,构建了一种新型的 20nm 纳米复合材料 Ag/C225,它由银纳米颗粒(AgNPs)与表皮生长因子受体特异性抗体(C225)偶联而成。物理特性表明,Ag/C225 纳米颗粒呈球形且在水中分散良好。酶联免疫吸附试验表明,Ag/C225 纳米颗粒中保留了 C225 的活性。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐分析的结果表明,AgNPs 和 Ag/C225 以剂量和时间依赖的方式抑制鼻咽癌细胞上皮(CNE)的增殖。流式细胞术显示,AgNPs 和 Ag/C225 诱导 CNE 凋亡,并阻止 G2 期阻滞;与 AgNPs 相比,Ag/C225 的这种作用更为明显。集落形成实验表明,AgNPs 和 Ag/C225 增加了 CNE 对辐射的敏感性。AgNPs 和 Ag/C225 的增敏比分别为 1.610±0.012 和 1.405±0.033 Gy。Western blot 分析表明,X 射线照射联合使用 AgNPs 或 Ag/C225 可降低 DNA 损伤/修复蛋白 Ku-70、Ku-80 和 Rad51 的表达水平;在这种情况下,Ag/C225 比 AgNPs 更有效。这些结果表明,AgNPs 和 Ag/C225 可有效增强 CNE 细胞的放射敏感性。因此,这些有效的药物可考虑在治疗人类鼻咽癌时用作放射增敏剂。

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