A self-assembly nanodrug delivery system based on amphiphilic low generations of PAMAM dendrimers-ursolic acid conjugate modified by lactobionic acid for HCC targeting therapy
A self-assembly nanodrug delivery system based on amphiphilic low generations of PAMAM dendrimers-ursolic acid conjugate modified by lactobionic acid for HCC targeting therapy
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基于乳糖酸修饰的两亲低代 PAMAM 树枝状聚合物-熊果酸缀合物的自组装纳米药物递送系统，用于 HCC 靶向治疗
DOI：
10.1016/j.nano.2017.10.007
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发表时间：
2018-02-01
影响因子：
5.4
通讯作者：
Shao, Jingwei
中科院分区：
文献类型：
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作者：
Shen, Zhichun;Li, Bowen;Shao, Jingwei
熊果酸(UA)是一种天然三萜酸，具有抑制肿瘤生长和转移的作用，是一种很有前途的抗癌药物。然而，尿酸的水溶性差，生物利用度低，限制了尿酸的临床翻译。为了克服这些问题，本文开发了一种由UA、乳糖酸(LA)和低聚酰胺胺(Low-PAMAM)树枝状大分子组成的两亲性自组装纳米片。这种近球形的纳米微球尺寸均匀(接近180 nm)，对肝癌SMMC7721细胞具有增强的细胞毒作用，并可通过抑制转移相关蛋白MMP9的表达，在无毒浓度下减弱SMMC7721细胞的迁移和黏附。体内实验表明，纳米微球能延长血液循环时间，增加AUC、MRT和C-max，并能有效抑制H22小鼠模型的肿瘤生长。总体而言，本研究报告的基于尿酸的纳米地毯递送系统代表了靶向肿瘤治疗的一种新策略。(C)2017 Elsevier Inc.保留所有权利。
Ursolic acid (UA), a natural triterpene acid, is a promising anti-cancer drug due to its inhibitory effect on tumor growth and metastasis. However, clinical translation of UA is limited by its poor water solubility and low bioavailability. To overcome these problems, herein an amphiphilic self-assembly nanodrug composed of UA, lactobionic acid (LA) and low-polyamidoamine (low-PAMAM) dendrimers is developed. This near-spherical nanodrug with a uniform size (similar to 180 nm) demonstrated to have an enhanced cytotoxicity against liver cancer SMMC7721 cells, and could attenuate the migration and adhesion of SMMC7721 cells at non-toxic concentrations by suppressing metastasis-related protein MMP-9 expression. Furthermore, in vivo study indicates that the nanodrug exhibited prolonged circulation time in blood as well as increased AUC, MRT and C-max, and could effectively inhibit the tumor growth in H22 mice model. Overall, the UA-based nanodrug delivery system reported in the present work represents a novel strategy for targeted tumor therapy. (c) 2017 Elsevier Inc. All rights reserved.