Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer.
Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer.
复制标题
DOI：
10.1007/s11095-014-1602-1
复制
发表时间：
2015-06
影响因子：
3.7
通讯作者：
Duan, Zhenfeng
中科院分区：
文献类型：
--
作者：
Yang, Xiaoqian;Iyer, Arun K.;Singh, Amit;Milane, Lara;Choy, Edwin;Hornicek, Francis J.;Amiji, Mansoor M.;Duan, Zhenfeng
用于合成生物材料以促进“生物制剂”的递送的方法是癌症治疗研究的主要领域。在这里，我们设计并表征了一种基于透明质酸（HA）的自组装纳米颗粒，它可以靶向多药耐药（MDR）卵巢癌上过表达的CD 44受体。该纳米颗粒系统由HA-聚（乙烯亚胺）/HA-聚（乙二醇）（HA-PEI/HA-PEG）组成，旨在递送MDR 1 siRNA，用于治疗卵巢癌模型中的MDR。制备并表征HA-PEI/HA-PEG/MDR 1 siRNA纳米粒，进一步测定其细胞摄取和敲减效率。建立人异种移植MDR卵巢癌模型以评估HA-PEI/HA-PEG/MDR 1 siRNA纳米颗粒和紫杉醇的组合对MDR肿瘤生长的作用。我们的结果表明，HA-PEI/HA-PEG纳米颗粒成功靶向CD 44并将MDR 1 siRNA递送到OVCAR 8 TR（已建立的紫杉醇耐药）肿瘤中。此外，HA-PEI/HA-PEG纳米颗粒负载MDR 1 siRNA有效地下调MDR 1和P-糖蛋白（Pgp）的表达，抑制Pgp的功能活性，并随后增加细胞对紫杉醇的敏感性。HA-PEI/HA-PEG/MDR 1 siRNA纳米颗粒疗法随后紫杉醇治疗抑制MDR卵巢癌小鼠模型中的肿瘤生长。这些发现表明，这种靶向CD 44的HA-PEI/HA-PEG纳米颗粒平台可能是用于治疗MDR癌症的基于siRNA的全身性抗癌疗法的临床相关基因递送系统。
Approaches for the synthesis of biomaterials to facilitate the delivery of “biologics” is a major area of research in cancer therapy. Here we designed and characterized a hyaluronic acid (HA) based self-assembling nanoparticles that can target CD44 receptors overexpressed on multidrug resistance (MDR) ovarian cancer. The nanoparticle system is composed of HA-poly(ethyleneimine)/HA-poly(ethylene glycol) (HA-PEI/HA-PEG) designed to deliver MDR1 siRNA for the treatment of MDR in an ovarian cancer model. HA-PEI/HA-PEG nanoparticles were synthesized and characterized, then the cellular uptake and knockdown efficiency of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles was further determined. A human xenograft MDR ovarian cancer model was established to evaluate the effects of the combination of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles and paclitaxel on MDR tumor growth. Our results demonstrated that HA-PEI/HA-PEG nanoparticles successfully targeted CD44 and delivered MDR1 siRNA into OVCAR8TR (established paclitaxel resistant) tumors. Additionally, HA-PEI/HA-PEG nanoparticles loaded with MDR1 siRNA efficiently down-regulated the expression of MDR1 and P-glycoprotein (Pgp), inhibited the functional activity of Pgp, and subsequently increased cell sensitivity to paclitaxel. HA-PEI/HA-PEG/MDR1 siRNA nanoparticle therapy followed by paclitaxel treatment inhibited tumor growth in MDR ovarian cancer mouse models. These findings suggest that this CD44 targeted HA-PEI/HA-PEG nanoparticle platform may be a clinicaly relevant gene delivery system for systemic siRNA-based anticancer therapeutics for the treatment of MDR cancers.
登录
查看更多内容
影响因子：
14
作者：
Ganesh, Shanthi;Iyer, Arun K.;Morrissey, David V.;Amiji, Mansoor M.
通讯作者：
Amiji, Mansoor M.
DOI：
10.1038/nrc2644
发表时间：
2009-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.9
作者：
Jiang, Ge;Park, Kitae;Hahn, Sei Kwang
通讯作者：
Hahn, Sei Kwang
影响因子：
7.5
作者：
Donmez, Yaprak;Gunduz, Ufuk
通讯作者：
Gunduz, Ufuk
影响因子：
11.5
作者：
Duan, Zhenfeng;Zhang, Jianming;Hornicek, Francis J.
通讯作者：
Hornicek, Francis J.