Zhao Yilin, Cai Fuli, Shen Xiangyi, Su Haijia
Beijing Key Laboratory of Bioprocess, Beijing University of Chemical Technology(BUCT), 15 BeiSanhuan East Road, ChaoYang District, Beijing, 100029, PR China.
Synth Syst Biotechnol. 2020 Jun 14;5(2):103-110. doi: 10.1016/j.synbio.2020.05.004. eCollection 2020 Jun.
In order to improve the targeting and availability of liposomes to cancer cells, the temperature sensitivity of 1, 2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and the pH sensitivity of PASP in PASP-g-C8 are incorporated in a drug delivery system. A composite pH-temperature dual-sensitive liposomes (CPTLPs) was obtained as an efficient drug delivery system. The bionic bilayer is self-assembled by cholesterol/cationic temperature-sensitive lipids as base layer and pH-sensitive octylamine grafted poly aspartic acid (PASP-g-C8) as anchors coated outside. Cytarabine (CYT) was chosen as a model drug. SEM and DLS were used to observe the morphology characteristics of CPTLPs in different micro environment. The results demonstrated that the CPTLPs remained active in both normal (pH7.4 and 37 °C) and tumor tissues (pH 5.0 and 42 °C). As a stable colloidal system, the zeta potential of CPTSLs was -41.6 mV. In vitro drug-release experiments, the CTY encapsulated dual-sensitive liposomes, CPTSLs(+), not only have significant pH-temperature sensitivity but have more prolonged release in vitro than control groups. MTT tests results indicated that the cell apoptotic effects induced by CPTSLs(+) were nearly 30% higher than the naked drug CTY in HepG2 cells, and 20% lower apoptotic in vero cells. The CPTSLs(+) sustained a stable emulsion form, less toxic effects on normal cells, and exhibited a good pH-temperature sensitivity, thus expected to be a promising tumor targeting drug delivery.
为了提高脂质体对癌细胞的靶向性和可用性，将1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）的温度敏感性和聚天冬氨酸接枝C8（PASP-g-C8）中PASP的pH敏感性整合到药物递送系统中。制备了一种复合pH-温度双敏感脂质体（CPTLPs）作为高效药物递送系统。仿生双层由胆固醇/阳离子温度敏感脂质自组装为基层，外部包覆pH敏感的辛胺接枝聚天冬氨酸（PASP-g-C8）作为锚定物。选择阿糖胞苷（CYT）作为模型药物。利用扫描电子显微镜（SEM）和动态光散射（DLS）观察CPTLPs在不同微环境中的形态特征。结果表明，CPTLPs在正常（pH7.4和37°C）和肿瘤组织（pH 5.0和42°C）中均保持活性。作为一种稳定的胶体系统，CPTSLs的ζ电位为-41.6 mV。在体外药物释放实验中，包封CYT的双敏感脂质体CPTSLs(+)不仅具有显著的pH-温度敏感性，而且在体外的释放时间比对照组更长。MTT试验结果表明，CPTSLs(+)诱导的细胞凋亡效应在HepG2细胞中比游离药物CYT高近30%，在vero细胞中的凋亡率低20%。CPTSLs(+)保持稳定的乳液形式，对正常细胞毒性较小，并表现出良好的pH-温度敏感性，因此有望成为一种有前景的肿瘤靶向药物递送载体。
