Development of self-assembling peptide nanovesicle with bilayers for enhanced EGFR-targeted drug and gene delivery
Development of self-assembling peptide nanovesicle with bilayers for enhanced EGFR-targeted drug and gene delivery
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DOI：
10.1016/j.biomaterials.2015.12.015
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发表时间：
2016-03-01
期刊：
影响因子：
14
通讯作者：
Li, Zonghai
中科院分区：
文献类型：
--
作者：
Liang, Xiaofei;Shi, Bizhi;Li, Zonghai
开发合理的载体用于有效的药物和基因递送对于癌症治疗是至关重要的。本研究以表皮生长因子受体（EGFR）结合肽两亲物（PA）为主要双层骨架材料，构建了超稳定的自组装肽纳米囊泡（SPV）。所得到的EGFR靶向SPV（ESPV）可以有效地封装治疗性货物（药物或小干扰RNA [siRNA]）或标记的荧光货物（量子点[QD]），并且对EGFR阳性癌细胞表现出优异的亲和力。此外，ESPV可以将更多的药物或质粒DNA递送到肿瘤部位并促进基因表达（ESPV与阳离子脂质体的三倍比例）。值得注意的是，通过ESPV单独递送或共同递送多柔比星（DOX）和乙酰胆碱酯酶（AChE）基因在体外和体内都产生了优异的药物/基因递送，并对肝癌异种移植物产生了显著的生长抑制作用。这种纳米级的靶向货物包装技术可能为设计高度靶向的癌症治疗载体提供新的策略。(C)2015爱思唯尔有限公司版权所有。
Development of rational vectors for efficient drug and gene delivery is crucial for cancer treatment. In this study, epidermal growth factor receptor (EGFR)-binding peptide amphiphile (PA) were used as the primary bilayer skeleton material to construct ultra-stable self-assembling peptide nanovesicle (SPV). The resulted EGFR-targeted SPV (ESPV) could efficiently encapsulate therapeutic cargos (drugs or small interfering RNAs [siRNAs]) or labelled fluorescent cargo (quantum dots [QDs]) and exhibited excellent affinity for EGFR-positive cancer cells. Moreover, ESPV could deliver more drug or plasmid DNA to tumour sites and promote gene expression (a three-fold ratio of ESPVs vs cationic liposomes). Notably, the individual delivery or co-delivery of doxorubicin (DOX) and the acetylcholinesterase (AChE) gene via the ESPVs resulted in excellent drug/gene delivery both in vitro and in vivo and exerted a significant growth-suppressing effect on a liver cancer xenograft. This nanoscale, targeted cargo-packaging technology may provide a new strategy for the design of highly targeted cancer therapy vectors. (C) 2015 Elsevier Ltd. All rights reserved.