文献：Ditelluride-Bridged PEG-PCL Copolymer as Folic Acid-Targeted and Redox-Responsive Nanoparticles for Enhanced Cancer Therapy

文献链接：https://xueshu.baidu.com/usercenter/paper/show?paperid=1q3a0rs05g5t0pe0k76n0mc009620641&site=xueshu_se

作者：Zekun Pang, Jiayan Zhou and Chunyang Sun

相关产品：FA-PEG-b-PCL

原文摘要：The development of the nanosized delivery systems with targeting navigation and efficient cargo release for cancer therapy has attracted great attention in recent years. Herein, a

folic acid (FA) modified PEGylated polycaprolactone containing ditelluride linkage was synthesized through a facile coupling reaction. The hydrophobic doxorubicin (DOX) can be encapsulated into the polymeric micelles, and such nanoparticles (F-TeNPDOX) exhibited redox-responsive drug release under abundant glutathione (GSH) condition due to the degradation of ditelluride bonds. In addition, flow cytometric analyses showed that the FA ligands on F-TeNPDOX could facilitate their cellular uptake in 4T1 breast cancer cells. Therefore, F-TeNPDOX led to the promoted drug accumulation and enhanced growth inhibition on 4T1 tumor in vivo. The obtained results suggest F-TeNPDOX excellent potential as nanocarriers for anticancer drug delivery.

FA-PEG-b-PCL（叶酸-聚乙二醇-b-聚己内酯）具有良好的生物相容性，其对生物体的副作用小。其中的聚乙二醇增加亲水性，提高稳定性并延长在体内的循环时间。聚己内酯可降解，降低对环境的负担。叶酸的引入赋予其主动靶向性，能将化合物输送至特定细胞。此外，该材料可修饰性强，能结合多种化合物或标记物。通过一种简易的偶联反应合成了一种含有二碲化物键的叶酸（FA）修饰的聚乙二醇化聚己内酯。疏水阿霉素（DOX）可以被封装在聚合物胶束中，这些纳米颗粒（F-TeNPDOX）在丰富的谷胱甘肽（GSH）条件下由于降解，表现出氧化还原反应性化合物释放。以下是制备过程：

图：F-TeNPDOX在4T1细胞上的细胞内化。DAPI（蓝色）和Alexa Fluor 488菌素（绿色）分别用于细胞核和f-肌动蛋白染色。比例尺为20µm。

载化合物纳米颗粒的制备

将PEG-b-PCL、FA-PEG-b-PCL和FA-PEGTeTe-PCL和DOX混合在DMSO中，搅拌。然后在剧烈搅拌下滴加入ddH2O，再保存通过透析管（MWCO =中的超纯水透析14000）去除有机相。离心，进一步去除游离的DOX。所获得的纳米颗粒分别用NPDOX、F-NPDOX和F-TeNPDOX表示。FA-PEG-TeTe-PCL、FA-PEG-b-PCL和PEG-b-PCL可以在水溶液中自组装成胶束纳米颗粒，然后有效地将疏水DOX封装在疏水核中。所制备的胶束分别用FTeNPDOX、F-NPDOX和NPDOX表示。采用480 nm紫外-可见分光光度计波长法测定DOX加载含量。

图：F-TeNPDOX的尺寸分布和形貌

结论：在本研究中，通过FA-PEG-b-PCL共聚物成功制备了一种靶向和氧化还原反应递送系统二碲化物连锁。获得的纳米颗粒能有效地装载疏水DOX，并表现出细胞内GSH触发的快速化合物释放。此外，F-TeNPDOX可以通过fa介导的内吞作用有效地内化到4T1细胞中，并在氧化还原反应性胶束解离后获得足够的“活性化合物”含量。此外，流式细胞仪分析显示，F-TeNPDOX上的FA配体可以促进其摄取。