Ji Xiaoting, Zhang Ruiyuan, Wang Zhenbo, Niu Shuyan, Ding Caifeng
Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education; Shandong Key Laboratory of Biochemical Analysis; Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong; College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, PR China.
ACS Appl Bio Mater. 2019 Jan 22;2(1):370-377. doi: 10.1021/acsabm.8b00623. Epub 2018 Dec 14.
Herein, we constructed a multifunctional spherical nanomicelle drug delivery system to improve the efficiency of cell uptake. The paclitaxel (PTX)-locked nucleic acid (LNA) monomer and the carboxyfluorescein (FAM)-labeled DNA were mixed together to assemble and form a spherical nanomicelle that was functionalized with transactivator of transcription (TAT), a cell-penetrating peptides (CPPs). A bioreductively activated disulfide was used to link the hydrophobic PTX to the LNA, allowing the PTX to be released freely in the presence of glutathione (GSH) upon cell uptake. Based on magnetic separation, the synthetic process of PTX-LNA monomers avoids time-consuming and labor-intensive shortcomings. Cellular uptake of PTX-LNA-TAT nanomicelle and the drug release occur rapidly as proved by fluorescence microscopy and flow cytometry. The resulting nanomicelle was greater stability, monodisperse size, and the high therapeutic potential. Furthermore, the system can readily achieve detection of GSH in the cancer cells. The detection limit for commercial GSH determined was 1.0 × 10 M by using PTX/Fluorescein isothiocyanate (FITC)-LNA/black hole quencher 1 (BHQ-1) as a probe.
在此，我们构建了一种多功能球形纳米胶束药物递送系统，以提高细胞摄取效率。将紫杉醇（PTX）锁定核酸（LNA）单体与羧基荧光素（FAM）标记的DNA混合在一起进行组装，形成一种用转录激活因子（TAT，一种细胞穿透肽（CPPs））功能化的球形纳米胶束。使用生物还原激活的二硫键将疏水性PTX与LNA连接，使PTX在细胞摄取后在谷胱甘肽（GSH）存在下自由释放。基于磁分离，PTX-LNA单体的合成过程避免了耗时且费力的缺点。荧光显微镜和流式细胞术证明，PTX-LNA-TAT纳米胶束的细胞摄取和药物释放迅速发生。所得纳米胶束具有更高的稳定性、单分散尺寸和高治疗潜力。此外，该系统能够轻松实现癌细胞中GSH的检测。使用PTX/异硫氰酸荧光素（FITC）-LNA/黑洞猝灭剂1（BHQ-1）作为探针测定的商业GSH检测限为1.0×10 M。
