pH-responsive hybrid nanoparticle with enhanced dissociation characteristic for siRNA delivery.
pH-responsive hybrid nanoparticle with enhanced dissociation characteristic for siRNA delivery.
复制标题
pH 响应性混合纳米颗粒，具有增强的 siRNA 递送解离特性
DOI：
10.2147/ijn.s180119
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发表时间：
2018
影响因子：
8
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Shi M;Zhao X;Zhang J;Pan S;Yang C;Wei Y;Hu H;Qiao M;Chen D;Zhao X
用小界面RNA（siRNA）沉默特异性polo样激酶（PLK 1）可能是治疗PLK 1过表达肺癌的有效方法。然而，低浓度的siRNA进入肿瘤组织的细胞质严重限制了它的应用。材料与方法本研究合成了一种新型的三嵌段共聚物mPEG-PHis-PSD（mPEG-PHis-PSD，简称PHD），并将其与阳离子脂质体一起构建新型的非病毒基因载体。结果制备的载siPLK 1的杂化纳米粒（PHD/LR）具有良好的理化性质。体外研究表明，PHD/LR可有效地内化入人肺腺癌A549细胞，并下调PLK 1蛋白表达，诱导细胞凋亡，这可能与PHD共聚物诱导的瞬时解离、有效的内/溶酶体逃逸有关。体内抗肿瘤实验表明，PHD/LR能有效地在肿瘤组织中蓄积，并沉默PLK 1的表达，具有抗肿瘤活性。结论PHD/LR有望成为肺癌特异性siRNA载体。
Introduction Specific polo-like kinase (PLK1) silencing with small interface RNA (siRNA) may be an effective approach for PLK1-overexpressed lung cancer. However, low siRNA concentration into cytoplasm of tumor tissue severely limits its application. Materials and methods In this study, a novel triblock copolymer methoxy poly(ethylene glycol)-poly(histidine)-poly(sulfadimethoxine) (mPEG-PHis-PSD, shorten as PHD) was synthesized and used to construct novel nonviral gene vector with cationic liposomes. Results The resulting hybrid nanoparticles (PHD/LR) loaded with siPLK1 possessed excellent physiochemical properties. In vitro study indicated that PHD/LR could be efficiently internalized into human lung adenocarcinoma A549 cells and downregulated PLK1 protein expression to induce cell apoptosis, which was attributed to pH-induced instantaneous dissociation, efficient endo/lysosomal escape arose from PHD copolymer. Furthermore, in vivo antitumor activity demonstrated that PHD/LR could efficiently accumulated into tumor tissue and silenced PLK1 expression to possess antitumor activity. Conclusion Taken all these together, PHD/LR was expected to be a suitable carrier for specific delivering siRNA for lung cancer therapy.