LAPONITE-Polyethylenimine Based Theranostic Nanoplatform for Tumor-Targeting CT Imaging and Chemotherapy.
LAPONITE-Polyethylenimine Based Theranostic Nanoplatform for Tumor-Targeting CT Imaging and Chemotherapy.
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DOI：
10.1021/acsbiomaterials.6b00528
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发表时间：
2017-01
影响因子：
5.8
通讯作者：
Zhuang Ying;Lingzhou Zhao;Lin-feng Zheng;Yong Hu;Ling Ding;Xin Li;Chang-cun Liu;Jinhua Zhao;Xiangyang Shi;Rui Guo
中科院分区：
文献类型：
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作者：
Zhuang Ying;Lingzhou Zhao;Lin-feng Zheng;Yong Hu;Ling Ding;Xin Li;Chang-cun Liu;Jinhua Zhao;Xiangyang Shi;Rui Guo
在这项研究中，合成锂皂石（Laponite）纳米盘和聚乙烯亚胺（PEI）被用来建立一个混合治疗诊断纳米平台，用于过表达CD 44受体的癌细胞的靶向计算机断层扫描（CT）成像和化疗。首先，通过疏水作用将两亲性共聚物聚乳酸-聚乙二醇（PLA-PEG-COOH）组装到纳米盘表面，然后通过1-乙基-3-（3-（二甲氨基）丙基）碳二亚胺（EDC）偶联反应将PEI偶联到纳米盘表面。将开发的LAP-PLA-PEG-PEI纳米颗粒用作包埋金纳米颗粒（Au NPs）的模板，然后用透明质酸（HA）修饰作为过表达CD 44受体的癌细胞的靶向配体。最后，装载抗癌药物多柔比星（DOX）。LAP-PLA-PEG-PEI-（Au 0）50-HA/DOX纳米复合物具有良好的稳定性，载药率高达91.0 ± 1.8%，并具有pH敏感性的缓释特性。体外细胞活力测定、流式细胞术分析和激光扫描共聚焦显微镜观察表明，所形成的纳米复合物可以特异性地递送并抑制过表达CD 44受体的癌细胞。体内实验表明，LAP-PLA-PEG-PEI-（Au 0）50-HA/DOX纳米复合物不仅能显著抑制肿瘤生长，减少DOX的毒副作用，而且可作为肿瘤CT成像的靶向造影剂。因此，开发的LAP-PLA-PEG-PEI-（Au 0）50-HA/DOX纳米复合物可用作有前景的治疗诊断平台，用于CD 44过表达肿瘤的靶向成像和化疗。
In this study, laponite (LAP) nanodisks and polyethylenimine (PEI) were used to build a hybrid theranostic nanoplatform for targeted computed tomography (CT) imaging and chemotherapy of cancer cells overexpressing CD44 receptors. First, amphiphilic copolymer poly(lactic acid)-poly(ethylene glycol) (PLA-PEG-COOH) were assembled on the surface of LAP nanodisks via hydrophobic interaction, and then PEI were conjugated by the formation of amide groups via1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) coupling chemistry. The developed LAP-PLA-PEG-PEI nanoparticles were used as templates for the embedding of gold nanoparticles (Au NPs), followed by modification with hyaluronic acid (HA) as a targeting ligand for cancer cells overexpressing CD44 receptors. Finally, anticancer drug doxorubicin (DOX) was loaded. The formed LAP-PLA-PEG-PEI-(Au0)50-HA/DOX nanocomplexes display good stability, a high drug loading efficiency as 91.0 ± 1.8%, and sustained drug release profile with a pH-sensitive manner. In vitro cell viability assay, flow cytometric analysis, and laser scanning confocal microscopy observation demonstrate that the formed nanocomplexes can specifically deliver and inhibit cancer cells overexpressing CD44 receptors. In vivo experiments illustrate that LAP-PLA-PEG-PEI-(Au0)50-HA/DOX nanocomplexes can not only significantly inhibit the growth of tumors and decrease the side-effect of DOX, but also be used as a targeted contrast agent for CT imaging of tumors. Therefore, the developed LAP-PLA-PEG-PEI-(Au0)50-HA/DOX nanocomplexes can be used as a promising theranostic platform for targeted imaging and chemotherapy of CD44-overexpressed tumors.