Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641 046, TN, India.
Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641 046, TN, India; Department of Virology, King Institute of Preventive Medicine and Research, Guindy, Chennai 600 032, TN, India.
Toxicol Appl Pharmacol. 2014 Mar 15;275(3):232-43. doi: 10.1016/j.taap.2014.01.012. Epub 2014 Jan 25.
Epidermal growth factor receptor antibody (EGFRAb) conjugated silica nanorattles (SNs) were synthesized and used to develop receptor mediated endocytosis for targeted drug delivery strategies for cancer therapy. The present study determined that the rate of internalization of silica nanorattles was found to be high in lung cancer cells when compared with the normal lung cells. EGFRAb can specifically bind to EGFR, a receptor that is highly expressed in lung cancer cells, but is expressed at low levels in other normal cells. Furthermore, in vitro studies clearly substantiated that the cPLA2α activity, arachidonic acid release and cell proliferation were considerably reduced by pyrrolidine-2 loaded EGFRAb-SN in H460 cells. The cytotoxicity, cell cycle arrest and apoptosis were significantly induced by the treatment of pyrrolidine-2 loaded EGFRAb-SN when compared with free pyrrolidine-2 and pyrrolidine-2 loaded SNs in human non-small cell lung cancer cells. An in vivo toxicity assessment showed that silica nanorattles and EGFRAb-SN-pyrrolidine-2 exhibited low systemic toxicity in healthy Balb/c mice. The EGFRAb-SN-pyrrolidine-2 showed a much better antitumor activity (38%) with enhanced tumor inhibition rate than the pyrrolidine-2 on the non-small cell lung carcinoma subcutaneous model. Thus, the present findings validated the low toxicity and high therapeutic potentials of EGFRAb-SN-pyrrolidine-2, which may provide a convincing evidence of the silica nanorattles as new potential carriers for targeted drug delivery systems.
表皮生长因子受体抗体（EGFRAb）偶联二氧化硅纳米笼（SNs）被合成并用于开发受体介导的内吞作用，以实现癌症治疗的靶向药物输送策略。本研究确定，与正常肺细胞相比，肺癌细胞中二氧化硅纳米笼的内化率较高。EGFRAb 可以特异性结合 EGFR，EGFR 是肺癌细胞中高度表达的受体，但在其他正常细胞中表达水平较低。此外，体外研究清楚地证实，在 H460 细胞中，载有吡咯烷-2 的 EGFRAb-SN 可显著降低 cPLA2α 活性、花生四烯酸释放和细胞增殖。与游离吡咯烷-2 和载有吡咯烷-2 的 SNs 相比，载有吡咯烷-2 的 EGFRAb-SN 对人非小细胞肺癌细胞的细胞毒性、细胞周期停滞和凋亡有显著诱导作用。体内毒性评估表明，二氧化硅纳米笼和 EGFRAb-SN-吡咯烷-2 在健康 Balb/c 小鼠中表现出低系统毒性。与非小细胞肺癌皮下模型中的吡咯烷-2 相比，EGFRAb-SN-吡咯烷-2 显示出更好的抗肿瘤活性（38%），肿瘤抑制率更高。因此，本研究结果验证了 EGFRAb-SN-吡咯烷-2 的低毒性和高治疗潜力，这可能为二氧化硅纳米笼作为新型靶向药物输送系统的潜在载体提供令人信服的证据。
