Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000 Sofia, Bulgaria.
Biomater Sci. 2018 Nov 20;6(12):3309-3317. doi: 10.1039/c8bm00644j.
Targeting tumor cell mitochondria is a prospective strategy for highly effective anticancer therapy. Consequently, the development of potent systems for the targeted delivery of mitochondria-acting therapeutics to mitochondria has the potential to boost this sector of nanomedicine. In this study, a functional mixed micellar system based on two co-assembled triblock copolymers, poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) bearing triphenylphosphonium ligands (PDMAEMA(TPP+)20-b-PCL70-b-PDMAEMA(TPP+)20) and poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO113-b-PCL70-b-PEO113), was assessed for the mitochondria targeted delivery of curcumin. The high proapoptotic activity of the system and the sub-cellular mechanisms of cytotoxicity were demonstrated using a chemosensitive HL-60 cell line and its resistant alternative HL-60/DOX. Next, the successful localization of nanocarriers in mitochondria was proved by fluorescence microscopy with the aid of DAPI (4',6-diamidino-2-phenylindole) as a cellular localization tracker. The in vitro experiments revealed the great potential of the functional system developed for the targeted delivery of curcumin to mitochondria, causing programmed tumor cell death.
靶向肿瘤细胞线粒体是一种极具前景的高效抗癌治疗策略。因此，开发靶向传递线粒体作用治疗剂至线粒体的有效系统有可能推动这一纳米医学领域的发展。在这项研究中，构建了一种基于两种共组装的两亲性嵌段共聚物的功能性混合胶束系统，该共聚物由带三苯基膦配体的聚[2-(二甲氨基)乙基甲基丙烯酸酯]-b-聚(ε-己内酯)-b-聚2-(二甲氨基)乙基甲基丙烯酸酯和聚(乙二醇)-b-聚(ε-己内酯)-b-聚(乙二醇)(PEO113-b-PCL70-b-PEO113)组成，用于姜黄素的靶向线粒体传递。通过使用对化疗敏感的 HL-60 细胞系及其耐药的 HL-60/DOX 替代物，评估了该系统的高促凋亡活性和细胞毒性的亚细胞机制。接下来，通过使用 DAPI（4',6-二脒基-2-苯基吲哚）作为细胞定位示踪剂的荧光显微镜，证明了纳米载体在细胞内成功定位于线粒体。体外实验表明，所开发的靶向传递姜黄素至线粒体的功能系统具有巨大潜力，能够引发肿瘤细胞程序性死亡。
