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【答案】应助回帖
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yjy2430499: 金币+200, 翻译EPI+1, ★★★★★最佳答案, 辛苦啦 谢谢 2015-03-28 20:31:13
携载紫杉醇靶向多功能纳米粒子治疗脑胶质瘤的实验研究
Preparation,Characterization and in vitro Testing of Paclitaxol-Loaded Multifunctional Nanoparticles on Glioma Cells
摘要：目的：本研究旨在制备一种新型携载紫杉醇（PTX）多功能纳米颗粒，并研究其体外释药及其抗肿瘤特性。探讨其对脑胶质瘤细胞增殖抑制的相关机制,为其在祌经系统恶性肿瘤中的应用提供理论基础
Abstract: Aims: the purpose of this work is to prepare new multifunctional nanoparticles carrying paclitaxol , characterize its drug release and anti-tumor properties, and explore the mechanisms of cell proliferation inhibitory activities towards glioma cells in vitro. The findings may provide a basis for developing new therapeutic agents for the treatment of malignancies in the central nerve systems.
方法：制备超支化聚（胺-酯）-聚乳酸-二棕榈酰磷脂酰乙醇胺（HPAE-co-PLA/DPPE）纳米药物载体，通过双乳液和纳米沉淀法将抗肿瘤模型药物紫杉醇（PTX）封装到共聚物的纳米颗粒。选用U251细胞和C6细胞进行细胞培养，通过对加载PTX的纳米系统药物释放曲线的研究，利用CCK-8法检测加载紫杉醇纳米粒的体外肿瘤细胞毒性试验，利用流式细胞仪检测药物在肿瘤细胞内积累情况，共聚焦激光扫描显微镜（ CLSM ）监测装载PTX的纳米颗粒在肿瘤细胞内分布的研究。
Methods: Hyperbranched poly[(amine ester)-co-(D,L-lactide)]/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HAPE-co-PLA/DPPE) was synthesized, and used as building blocks for the preparartion of nanaoparticles. Paclitaxol, a model anti-cancer drug was loaded into nanoparticles using double emulsion and co-precipitation methods. The PTX-loaded nanoparticles were studied for its in vitro drug release properties. In vitro cytotoxicity were measured using U251 and C6 glioma cell lines by CCK-8 assays. Quantitative cellular uptake of these nanoparticles was assessed using Flow Cytometry. The intracelluar trafficking of these nanoparticles were monitored by confocal laser scanning microscopy.
结果：新型携载紫杉醇（PTX）多功能纳米颗粒（超支化聚（胺-酯）-聚乳酸-二棕榈酰磷脂酰乙醇胺（HPAE-co-PLA/DPPE）纳米药物载体）制备成功，携载紫杉醇（PTX）多功能纳米颗粒具有明显的细胞穿透特性，呈现缓释且pH敏感的体外药物释放特征，相比非靶向载药纳米胶束，肿瘤靶向修饰的载药纳米胶束能够更有效的抑制体外培养的细胞的生长，更迅速地穿透细胞膜并更多的在细胞内积累。可以明显提高药物的抗肿瘤活性。
Results: New PTX-loaded multifunctional HPAE-co-PLA/DPPE nanoparticles were successfully prepared. These nanoparticles readily entered cells and demonstrated pH-sensitive and slow release properties. Compared with a control PTX-nanoparticle formulation that was not target-selective, the multifunctional nanoparticles with tumor targeting modification became rapidly across cell membrane barriers and accumulated inside cells, resulted in more efficient inhibition on cell growth and potent anti-tumor activity in vitro .
结论：成功制备新型携载紫杉醇（PTX）多功能纳米颗粒，对靶向和非靶向载药纳米粒子跨膜行为的示踪实验显示，两种载药胶束通过不同的内吞途径进入细胞，但最终均聚积在溶酶体中。装载紫杉醇纳米粒子表现出对pH敏感性及有效的时间延迟细胞毒性。因此，该共聚物的纳米颗粒被证明是用于抗肿瘤的药物递送的可用载体，携载PTX后有较明显的抗肿瘤作用，值得进一步进行体内研究。
Conclusion: We have successfully prepared new PTX-loaded multifunctional nanoparticles. Cellular uptake studies revealed that targeted and non-targeted nanoparticles entered cells via different endocytosis pathways, though ultimately, both ended up in lysosomal compartments. We demonstrated that nanoparticles prepared from HAPE-co-PLA/DPPE copolymers can be used as a carrier for anti-cancer agents. PTX-loaded multifunctional nanoparticles exhibited pH-sensitive , slow release properties that resulted in more potent cytotoxicity, which warrants further in vivo testings.
关键词: 神经胶质瘤；紫杉醇；多功能纳米粒子；靶向
Key words: Gliomas, paclitaxol , multifunctional nanoparticles, target-specific |
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