摘要
目的制备钌配合物[Ru(dmp)2PFPIP]脂质体(Lipo-Ru),提高药物的抗肿瘤活性,阐明Lipo-Ru的细胞毒性和抗肿瘤作用机制。方法薄膜分散法制备Lipo-Ru,超速离心法测定包封率。激光粒度分析仪和扫描电子显微镜分析Lipo-Ru的形状和粒径。MTT法检测Lipo-Ru对He La细胞的体外细胞毒性,AO/EB染色法观察凋亡细胞的形态学变化。Image Xpress高内涵成像系统检测线粒体膜电位(ΔΨm),活性氧(ROS)变化情况。结果薄膜分散法制备的Lipo-Ru的包封率较高并且稳定性良好,具有较光滑的表面以及呈现近乎球形的形态;平均粒径、Zeta电位以及包封率分别是(351.6±10.6) nm、(-5.08±1.1) m V以及(90.1±0.7)%。Lipo-Ru具有较高的细胞毒性,对He La细胞的半数抑制浓度为15.96μmol·L^-1;Lipo-Ru作用于细胞使其出现凋亡形态学特征;Lipo-Ru可诱导活性氧含量增加,线粒体膜电位降低。结论以脂质体作为钌配合物的给药载体明显提高钌配合物对He La宫颈癌细胞的毒性。Lipo-Ru有望成为一种新的钌配合物给药系统,在临床上得到进一步应用。
OBJECTIVE Ruthenium complex [Ru(dmp)2 PFPIP]-loaded liposomes(Lipo-Ru) as a drug delivery system are prepared,and the anti-tumor effects and mechanism on He La cells are elucidated.METHODS Lipo-Ru were prepared by thin-film dispersion method,the encapsulation efficiency was determined by ultracentrifugation. Shape and particle size of Lipo-Ru were analyzed by laser particle size analyzer and scanning electron microscope.MTT assay was used to detect the in vitro cytotoxicity of Lipo-Ru on He La cells,and the morphological changes of apotosis cells were observed through AO/EB staining methods.The mitochondrial membrane potential(ΔΨm) and reactive oxygen species(ROS) were studied by using The ImageXpress high-content imaging system. RESULTS The encapsulation efficiency of Lipo-Ru prepared by thin-film dispersion method was high and the stability was good. Lipo-Ru had a smooth surface and almost spherical shape. The particle size,Zeta potential and encapsulation efficiency were(351.6±10.6)nm,(-5.08±1.1) m V and(90.1±0.7) %,respectively. Lipo-Ru were highly cytotoxic,with a 50% inhibitory concentration of 15.96 μmol·L^-1 on HeLa cells.Lipo-Ru acted on the cell and made it presented the morphological characteristics of apoptosis. Lipo-Ru could induce the increase of ROS content and decrease of mitochondrial membrane potential. CONCLUSION The toxicity of ruthenium complexes on HeLa cervical cancer cells is significantly improved by using liposomes as a drug delivery system. Therefore,Lipo-Ru are expected to become a new ruthenium complex drug delivery system and be further applied in clinic.
作者
李天舒
吴秀君
廖灿城
方宇奇
郭波红
LI Tianshu;WU Xiujun;LIAO Cancheng;FANG Yuqi;GUO Bohong(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou,Guangdong 510006,China;Department of Medicine,Guangdong Women and Children Hospital and Health Institute,Guangzhou,Guangdong 510010,China)
出处
《今日药学》
CAS
2019年第11期732-736,共5页
Pharmacy Today
基金
国家自然科学基金(81403111)
广州市科技计划项目(201904010112)
关键词
脂质体
钌配合物
细胞毒性
抗肿瘤机制
liposome
ruthenium complex
cytotoxicity
antitumor mechanism
