Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, 174 W 18th Avenue, Columbus, Ohio 43210, USA.
ACS Nano. 2012 Mar 27;6(3):2245-52. doi: 10.1021/nn204300s. Epub 2012 Feb 22.
Theranostic lipoplexes are an integrated nanotherapeutic system with diagnostic imaging capability and therapeutic functions. They hold great promise to improve current cancer treatments; however, producing uniform theranostic lipoplexes with multiple components in a reproducible manner is a highly challenging task. Conventional methods, such as bulk mixing, are not able to achieve this goal because of their macroscale and random nature. Here we report a novel technique, called the static micromixer-coaxial electrospray (MCE), to synthesize theranostic lipoplexes in a single step with high reproducibility. In this work, quantum dots (QD605) and Cy5-labeled antisense oligodeoxynucleotides (Cy5-G3139) were chosen as the model imaging reagent and therapeutic drug, respectively. Compared with bulk mixing, QD605/Cy5-G3139-loaded lipoplexes produced by MCE were highly uniform with polydispersity of 0.024 ± 0.006 and mean diameter by volume of 194 ± 15 nm. MCE also showed higher encapsulation efficiency of QD605 and Cy5-G3139. QD605 and Cy5 also formed the Förster resonance energy transfer pair, and thus the cellular uptake and intracellular fate of theranostic lipoplexes could be visualized by flow cytometry and confocal microscopy. The lipoplexes were efficiently delivered to A549 cells (non-small cell lung cancer cell line) and down-regulated the Bcl-2 gene expression by 48 ± 6%.
治疗诊断一体化脂质体是一种具有诊断成像能力和治疗功能的综合纳米治疗系统。它们有望改善当前的癌症治疗方法；然而，以可重复的方式生产具有多种成分的均匀治疗诊断一体化脂质体是一项极具挑战性的任务。由于其宏观尺寸和随机性质，传统方法（如批量混合）无法实现这一目标。在这里，我们报告了一种称为静态微混合-同轴电喷雾（MCE）的新技术，可一步高重复性地合成治疗诊断一体化脂质体。在这项工作中，量子点（QD605）和 Cy5 标记的反义寡脱氧核苷酸（Cy5-G3139）分别被选为模型成像试剂和治疗药物。与批量混合相比，通过 MCE 制备的 QD605/Cy5-G3139 负载的脂质体高度均匀，多分散性为 0.024 ± 0.006，体积平均直径为 194 ± 15nm。MCE 还显示出更高的 QD605 和 Cy5-G3139 的包封效率。QD605 和 Cy5 也形成了Förster 共振能量转移对，因此可以通过流式细胞术和共聚焦显微镜可视化治疗诊断一体化脂质体的细胞摄取和细胞内命运。脂质体有效地递送至 A549 细胞（非小细胞肺癌细胞系），并将 Bcl-2 基因表达下调了 48 ± 6%。
