A supramolecular nanoparticle system based on β-cyclodextrin-conjugated poly-L-lysine and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma
A supramolecular nanoparticle system based on β-cyclodextrin-conjugated poly-L-lysine and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma
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基于β-环糊精缀合的聚-L-赖氨酸和透明质酸的超分子纳米颗粒系统，用于共同递送针对肝细胞癌的基因和化疗药物
DOI：
10.1016/j.colsurfb.2017.04.008
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发表时间：
2017-07-01
影响因子：
5.8
通讯作者：
Song, Tianqiang
中科院分区：
文献类型：
--
作者：
Xiong, Qingqing;Cui, Mangmang;Song, Tianqiang
设计了一种基于β-环糊精偶联聚L-赖氨酸（PLCD）和透明质酸的核壳结构超分子纳米粒体系，用于肝癌靶向基因和化疗药物的共递送。通过单醛活化的β-环糊精与聚-L-赖氨酸通过Shift碱反应偶联来合成PLCD。以阿霉素为模型药物，通过主客体相互作用将其包合到β-环糊精的疏水空腔中。以oligoRNA为模型基因，通过静电相互作用将oligoRNA进一步凝聚到包合物中，形成了oligoRNA与阿霉素共载的超分子纳米粒体系。将肝癌细胞高表达的透明质酸包被在上述纳米粒表面，构建肝癌靶向纳米粒系统。这些纳米颗粒呈规则球形，具有经典的“核壳”结构，尺寸和zeta电位分别为195.8 nm和22.7 mV。纳米粒可通过CD 44受体介导的内吞作用将阿霉素和寡聚RNA有效地递送到肝癌细胞中，并显著抑制细胞增殖。在荷瘤裸鼠体内，纳米粒可在肿瘤组织中有效聚集，具有较强的肝癌靶向性。这些研究结果表明，这种新型的超分子纳米颗粒系统在联合基因治疗和化疗治疗肝癌方面具有很大的潜力。(C)2017爱思唯尔B. V.保留所有权利。
A novel supramolecular nanoparticle system with core-shell structure was designed based on beta-cyclodextrin-conjugated poly-L-lysine (PLCD) and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma (HCC). PLCD was synthesized by the conjugation of monoaldehyde activated beta-cyclodextrin with poly-L-lysine via Shift's base reaction. Doxorubicin, as a model therapeutic drug, was included into the hydrophobic cavity of beta-cyclodextrin in PLCD through host-guest interaction. OligoRNA, as a model gene, was further condensed into the inclusion complexes by electrostatic interaction to form oligoRNA and doxorubicin co-loaded supramolecular nanoparticle system. Hyaluronic acid, which is often over-expressed by HCC cells, was coated on the surface of the above nanoparticles to construct HCC-targeted nanoparticle system. These nanoparticles had regular spherical shape with classic "core-shell" structure, and their size and zeta potential were 195.8 nm and 22.7 mV, respectively. The nanoparticles could effectively deliver doxorubicin and oligoRNA into HCC cells via CD44 receptor-mediated endocytosis and significantly inhibit the cell proliferation. In the nude mice bearing MHCC-97H tumor, the nanoparticles could be efficiently accumulated in the tumor, suggesting their strong hepatoma-targeting capability. These findings demonstrated that this novel supramolecular nanoparticle system had a promising potential for combining gene therapy and chemotherapy to treat HCC. (C) 2017 Elsevier B.V. All rights reserved.