Liver-Targeted Combination Therapy Basing on Glycyrrhizic Acid-Modified DSPE-PEG-PEI Nanoparticles for Co-delivery of Doxorubicin and Bcl-2 siRNA
Liver-Targeted Combination Therapy Basing on Glycyrrhizic Acid-Modified DSPE-PEG-PEI Nanoparticles for Co-delivery of Doxorubicin and Bcl-2 siRNA
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基于甘草酸修饰 DSPE-PEG-PEI 纳米颗粒共同递送阿霉素和 Bcl-2 siRNA 的肝脏靶向联合治疗
DOI：
10.3389/fphar.2019.00004
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发表时间：
2019-01
影响因子：
5.6
通讯作者：
Wu Jingliang
中科院分区：
文献类型：
--
作者：
Tian Guixiang;Pan Ruiyan;Zhang Bo;Qu Meihua;Lian Bo;Jiang Hong;Gao Zhiqin;Wu Jingliang
基于纳米给药系统的联合治疗是一种将两种或两种以上抗肿瘤机制相结合的治疗策略。本研究制备了由1，2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-聚乙二醇-聚醚酰亚胺（DSPE-PEG-PEI）和大黄酸修饰的透明质酸（GA-HA）组成的肝靶向纳米粒（GH-DPP），用于阿霉素（DOX）和Bcl-2 siRNA的共递送。测定载药GH-DPP纳米粒（siRNA/DOX/GH-DPP）的粒径、ζ电位和形态。针对HepG 2细胞分析细胞摄取和体外细胞毒性。在H22荷瘤小鼠中评价siRNA/DOX/GH-DPP的体内生物分布和抗肿瘤治疗效果。结果表明，siRNA/DOX/GH-DPP纳米粒呈近球形，对HepG 2细胞具有剂量依赖性的细胞毒作用。与不含大黄酸的共递送系统（siRNA/DOX/DPP）和单独递送DOX或Bcl-2 siRNA的GH-DPP纳米粒相比，siRNA/DOX/GH-DPP纳米粒可诱导更多的细胞凋亡，显示出更高的抗肿瘤作用。GH-DPP纳米粒可以同时将化疗药物和siRNA递送到肿瘤区域，在抗肿瘤治疗中显示出巨大的潜力。
Combination therapy based on nano-sized drug delivery system has been developed as a promising strategy by combining two or more anti-tumor mechanisms. Here, we prepared liver-targeted nanoparticles (GH-DPP) composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-polyetherimide (DSPE-PEG-PEI) with Glycyrrhetinic acid-modified hyaluronic acid (GA-HA) for co-delivery of doxorubicin (DOX) and Bcl-2 siRNA. Particles size, zeta potential and morphology were determined for the drug-loaded GH-DPP nanoparticles (siRNA/DOX/GH-DPP). Cellular uptake and in vitro cytotoxicity were analyzed against HepG2 cells. In vivo bio-distribution and anti-tumor therapeutic effects of siRNA/DOX/GH-DPP were evaluated in H22-bearing mice. The results showed that siRNA/DOX/GH-DPP nanoparticles were nearly spherical and showed dose-dependent cytotoxicity against HepG2 cells. Compared to Glycyrrhetinic acid-free co-delivery system (siRNA/DOX/DPP) and GH-DPP nanoparticles for delivery of DOX or Bcl-2 siRNA alone, siRNA/DOX/GH-DPP nanoparticles could induce more cellular apoptosis, and showed higher anti-tumor effect. Herein GH-DPP nanoparticles could simultaneously deliver both chemotherapy drugs and siRNA into the tumor region, exhibiting great potential in anti-tumor therapy.
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影响因子：
7.4
作者：
Wei L;Lu J;Xu H;Patel A;Chen ZS;Chen G
通讯作者：
Chen G
用于肝癌药物输送的甘草次酸功能化纳米颗粒。
DOI：
10.1166/jbn.2018.2638
发表时间：
2018
期刊：
JBN
影响因子：
--
作者：
Wu F;Li X;Jiang B;Yan J;Zhang Z;Qin J;Yu W;Gao Z
通讯作者：
Gao Z
聚(乙烯亚胺)-甘草次酸纳米颗粒共同递送阿霉素和shAkt1诱导自噬介导的肝癌联合治疗
影响因子：
4.9
作者：
Wang, Feng-Zhen;Xing, Lei;Zong, Li
通讯作者：
Zong, Li
影响因子：
5.6
作者：
Zahreddine H;Borden KL
通讯作者：
Borden KL
影响因子：
5.6
作者：
Arms L;Smith DW;Flynn J;Palmer W;Martin A;Woldu A;Hua S
通讯作者：
Hua S