Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy
Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy
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DOI：
10.1016/j.biomaterials.2009.07.008
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发表时间：
2009-10-01
期刊：
影响因子：
14
通讯作者：
Sahoo, Sanjeeb K.
中科院分区：
文献类型：
--
作者：
Acharya, Sarbari;Dilnawaz, Fahima;Sahoo, Sanjeeb K.
选择性给药是一种重要的方法，具有很大的潜力，以克服与全身毒性和生物利用度差的药物相关的问题。纳米医学通过以靶向方式将药物递送到恶性肿瘤细胞从而降低抗癌药物的全身毒性而发挥关键作用。本研究的目的是制备和表征负载雷帕霉素的聚合物聚（丙交酯-共-乙交酯）（PLGA）纳米颗粒（NP），其表面与针对表皮生长因子受体（EGFR）的抗体结合，该EGFR在乳腺癌细胞上高度表达，使用1-乙基-3-（3-二甲氨基丙基）碳二亚胺盐酸盐（EDC）和N-羟基琥珀酰亚胺（NHS）介导的交联剂。为了增强制剂的抗癌效率，在恶性MCF 7乳腺癌细胞系上评估天然雷帕霉素、雷帕霉素负载的纳米颗粒和EGFR抗体缀合的雷帕霉素负载的纳米颗粒（EGFR-Rapa-NP）的体外细胞毒性。通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑（MTT）测定确定的IC 50剂量显示EGFR-Rapa-NP的抗增殖活性优于未缀合的纳米颗粒和天然雷帕霉素，这是由于恶性乳腺癌细胞的细胞摄取较高。通过流式细胞术证实上述制剂诱导的细胞周期停滞和细胞凋亡。通过蛋白质印迹法研究细胞凋亡的分子基础，揭示了细胞质蛋白参与激活程序性细胞死亡途径。因此，EGFR-Rapa-NPs可有效靶向递送抗癌药物，有望成为肿瘤选择性治疗的活性靶向载体。(C)2009爱思唯尔有限公司保留所有权利。
Selective drug delivery is an important approach with great potential for overcoming problems associated with the systemic toxicity and poor bioavailability of antineoplastic drugs. Nanomedicine plays a pivotal role by delivering drugs in a targeted manner to the malignant tumor cells thereby reducing the systemic toxicity of the anticancer drugs. The objective of this study was to prepare and characterize rapamycin loaded polymeric poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) that were surface conjugated with antibodies to epidermal growth factor receptor (EGFR), highly expressed on breast cancer cells, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) mediated cross linking agents. To potentiate the anticancer efficiency of the formulations, in vitro cytotoxicity of native rapamycin, rapamycin loaded nanoparticles and EGFR antibody conjugated rapamycin loaded nanoparticles (EGFR-Rapa-NPs) were evaluated on malignant MCF 7 breast cancer cell lines. IC50 doses as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay showed the superior antiproliferative activity of EGFR-Rapa-NPs over unconjugated nanoparticles and native rapamycin due to higher cellular uptake on malignant breast cancer cells. Cell cycle arrest and cellular apoptosis induced by the above formulations were confirmed by flow cytometry. Molecular basis of apoptosis studied by western blotting revealed the involvement of a cytoplasmic protein in activating the programmed cell death pathway. Thus it was concluded that EGFR-Rapa-NPs provide an efficient and targeted delivery of anticancer drugs, presenting a promising active targeting carrier for tumor selective therapeutic treatment in near future. (C) 2009 Elsevier Ltd. All rights reserved.