Han Xue, Su Ruijuan, Huang Xiuqing, Wang Yingli, Kuang Xiao, Zhou Shuang, Liu Hongzhuo
Shenyang Pharmaceutical University, Shenyang 110016, China.
Asian J Pharm Sci. 2019 Sep;14(5):569-580. doi: 10.1016/j.ajps.2018.06.006. Epub 2018 Sep 18.
Mitochondria are currently known as novel targets for treating cancer, especially for tumors displaying multidrug resistance (MDR). This present study aimed to develop a mitochondria-targeted delivery system by using triphenylphosphonium cation (TPP)-conjugated Brij 98 as the functional stabilizer to modify paclitaxel (PTX) nanocrystals (NCs) against drug-resistant cancer cells. Evaluations were performed on 2D monolayer and 3D multicellular spheroids (MCs) of MCF-7 cells and MCF-7/ADR cells. In comparison with free PTX and the non-targeted PTX NCs, the targeted PTX NCs showed the strongest cytotoxicity against both 2D MCF-7 and MCF-7/ADR cells, which was correlated with decreased mitochondrial membrane potential. The targeted PTX NCs exhibited deeper penetration on MCF-7 MCs and more significant growth inhibition on both MCF-7 and MCF-7/ADR MCs. The proposed strategy indicated that the TPP-modified NCs represent a potentially viable approach for targeted chemotherapeutic molecules to mitochondria. This strategy might provide promising therapeutic outcomes to overcome MDR.
线粒体目前被认为是治疗癌症的新靶点，尤其是对于表现出多药耐药性（MDR）的肿瘤。本研究旨在开发一种线粒体靶向递送系统，通过使用三苯基膦阳离子（TPP）共轭的Brij 98作为功能稳定剂来修饰紫杉醇（PTX）纳米晶体（NCs），以对抗耐药癌细胞。对MCF-7细胞和MCF-7/ADR细胞的二维单层和三维多细胞球体（MCs）进行了评估。与游离PTX和非靶向PTX NCs相比，靶向PTX NCs对二维MCF-7和MCF-7/ADR细胞均表现出最强的细胞毒性，这与线粒体膜电位降低相关。靶向PTX NCs在MCF-7 MCs上表现出更深的渗透，对MCF-7和MCF-7/ADR MCs均表现出更显著的生长抑制。所提出的策略表明，TPP修饰的NCs代表了一种将化疗分子靶向线粒体的潜在可行方法。该策略可能为克服MDR提供有前景的治疗效果。
