Mulberry-like dual-drug complicated nanocarriers assembled with apogossypolone amphiphilic starch micelles and doxorubicin hyaluronic acid nanoparticles for tumor combination and targeted therapy
Mulberry-like dual-drug complicated nanocarriers assembled with apogossypolone amphiphilic starch micelles and doxorubicin hyaluronic acid nanoparticles for tumor combination and targeted therapy
复制标题
阿朴酚两亲性淀粉胶束和阿霉素透明质酸纳米粒组装成类桑双药复合纳米载体，用于肿瘤联合靶向治疗。
DOI：
10.1016/j.biomaterials.2014.10.073
复制
发表时间：
2015-01-01
期刊：
影响因子：
14
通讯作者：
Wu, Daocheng
中科院分区：
文献类型：
--
作者：
Li, Ke;Liu, Hao;Wu, Daocheng
提出了一种制备高载药量、双药比例可调的桑葚状双药复合纳米载体的综合策略。首先，采用自组装技术制备了阿朴棉酚酮（ApoG 2）两亲性淀粉胶束（AASt MCs），并通过静电吸附法将过量的HA吸附到阿霉素（DOX）表面，制备了DOX透明质酸纳米粒（DHA NPs）。MLDC NC通过经由静电相互作用在一个AASt MC周围吸附8-9个DHA NP而获得。采用紫外-可见分光光度计和荧光分光光度计分别测定两种药物的包封率和载药量。用透射电镜和动态光散射法观察了粒子的粒径分布和形貌。通过体外细胞摄取和体内近红外荧光成像证实了HA受体介导引起的肿瘤靶向特征。发现MLDC NC具有桑葚状形状，动态尺寸为83.1 +/-6.6nm。MLDC NC中ApoG 2和DOX的最终包封率分别为94 +/- 1.7%和87 +/- 5.8%，载药量分别为13.3 +/- 1.2%和13.1 +/-3.7%。在80 h内几乎没有发现ApoG 2释放，即使在72 h后也只有不到30%的DOX释放到外相中。体内荧光成像显示MLDC NC在体内肿瘤处具有高效的靶向和蓄积，并且在小鼠静脉注射后维持96 h。急性毒性试验发现两种药物在MLDC NC中的LD 50较低。在MLDC NC中，1/5正常剂量的两种药物在减小肿瘤大小方面表现出显著高于游离药物组合或单独载药纳米颗粒的抗肿瘤效率，表明桑葚状双药物纳米平台在肿瘤治疗中具有巨大的潜力。(C)2014爱思唯尔有限公司版权所有。
A comprehensive strategy for the preparation of mulberry-like dual-drug complicated nanocarriers (MLDC NCs) with high drug loading and adjustable dual-drug ratio was developed. First, apogossypolone (ApoG2) amphiphilic starch micelles (AASt MCs) were prepared by self-assembly process, and doxorubicin (DOX) hyaluronic acid nanoparticles (DHA NPs) were prepared by DOX absorption with excess HA by electrostatic absorption. MLDC NCs were obtained by adsorption of 8-9 DHA NPs around one AASt MC via electrostatic interaction. UV-visible and fluorescence spectrophotometers were used to measure the entrapment efficiency and loading efficiency of the two drugs. Transmission electron microscope and dynamic light scattering method were used to observe the size distribution and morphology of the particles. The tumor-targeting feature caused by HA-receptor mediation was confirmed by in vitro cell uptake and in vivo near-infrared fluorescence imaging. MLDC NCs were found to possess a mulberry-like shape with a dynamic size of 83.1 +/- 6.6 nm. The final encapsulation efficiencies of ApoG2 and DOX in MLDC NCs were 94 +/- 1.7% and 87 +/- 5.8% with respect to drug-loading capacities of 13.3 +/- 1.2% and 13.1 +/- 3.7%, respectively. Almost no ApoG2 release was found within 80 h and less than 30% of DOX was released into the outer phase even after 72 h. In vivo fluorescence imaging revealed that MLDC NCs had highly efficient targeting and accumulation at the tumor in vivo and was maintained for 96 h after being injected intravenously in mice. Low LD50 for the two drugs in MLDC NCs was found after acute toxicity test. One-fifth normal dosage of the two drugs in MLDC NCs exhibited significantly higher anti-tumor efficiency in reducing tumor size compared with free drugs combination or single drug-loaded nanoparticles individually, indicating that the mulberry-like dual-drug nanoplatform has a great potential in tumor therapy. (C) 2014 Elsevier Ltd. All rights reserved.