Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy
Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy
复制标题
负载阿霉素的两亲性多肽纳米颗粒作为癌症治疗的有效药物递送系统
DOI：
10.1016/j.actbio.2013.08.015
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发表时间：
2013-12-01
影响因子：
9.7
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
--
作者：
Lv, Shixian;Li, Mingqiang;Chen, Xuesi
合成了一种具有三个功能化结构域的两亲性阴离子共聚物甲氧基聚乙二醇-b-聚（L-谷氨酸-co-L-苯丙氨酸）（mPEG-b-P（Glu-co-Phe）），并将其用作通过静电相互作用递送阳离子抗癌药物盐酸阿霉素（DOX-HCl）的纳米载体。这三个结构域显示出不同的功能：PEG嵌段链用于延长循环;聚（苯丙氨酸）结构域用于通过疏水/芳族相互作用稳定纳米颗粒构建体;聚（谷氨酸）结构域用于提供与待装载的阳离子药物的静电相互作用。该共聚物可以自组装成胶束型纳米粒子，并成功地装载到纳米粒子的内部DOX通过简单的混合DOX-HCl和共聚物在水相中。DOX-NP具有良好的上级载药量（DLC）（21.7%）、高的载药量（98%）和pH触发释放DOX。DOX-NP的尺寸类似于140 nm，如通过动态光散射测量和透射电子显微镜所确定的。体外实验表明，与游离DOX-HCl相比，DOX-NP在A549细胞系中表现出更高的细胞增殖抑制和更高的细胞摄取。最大耐受剂量（MTD）研究显示DOX-NP表现出优异的安全性特征，MTD（15 mg DOX kg（-1））显著高于游离DOX.HCl（5 mg DOX kg（-1））。在皮下非小细胞肺癌（A549）裸鼠移植瘤模型上的体内研究证实，DOX-NP显示出显著的抗肿瘤活性和降低的副作用，并且与游离DOX相比，由于延长了在血液中的循环和增强的渗透和滞留效应，从而增强了肿瘤蓄积，表明其具有巨大的癌症治疗潜力。(C)2013 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
An amphiphilic anionic copolymer, methoxy poly(ethylene glycol)-b-poly(L-glutamic acid-co-L-phenylalanine) (mPEG-b-P(Glu-co-Phe)), with three functionalized domains, was synthesized and used as a nanovehicle for cationic anticancer drug doxorubicin hydrochloride (DOX-HCl) delivery via electrostatic interactions for cancer treatment. The three domains displayed distinct functions: PEG block chain for prolonged circulation; poly(phenylalanine) domain for stabilizing the nanoparticle construct through hydrophobic/aromatic interactions; and the poly(glutamic acid) domain for providing electrostatic interactions with the cationic drug to be loaded. The copolymer could self-assemble into micellar-type nanoparticles, and DOX was successfully loaded into the interior of nanoparticles by simple mixing of DOX-HCl and the copolymer in the aqueous phase. DOX-loaded mPEG-b-P(Glu-co-Phe) nanoparticles (DOX-NP) had a superior drug-loading content (DLC) (21.7%), a high loading efficiency (almost 98%) and a pH-triggered release of DOX. The size of DOX-NP was similar to 140 nm, as determined by dynamic light scattering measurements and transmission electron microscopy. In vitro assays showed that DOX-NP exhibited higher cell proliferation inhibition and higher cell uptake in A549 cell lines compared with free DOX-HCl. Maximum tolerated dose (MTD) studies showed that DOX-NP demonstrated an excellent safety profile with a significantly higher MTD (15 mg DOX kg(-1)) than that of free DOX.HCl (5 mg DOX kg(-1)). The in vivo studies on the subcutaneous non-small cell lung cancer (A549) xenograft nude mice model confirmed that DOX-NP showed significant antitumor activity and reduced side effects, and then enhanced tumor accumulation as a result of the prolonged circulation in blood and the enhanced permeation and retention effect, compared with free DOX, indicating its great potential for cancer therapy. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.