FeS-PEG载药纳米颗粒对肿瘤细胞杀伤作用的研究

Study on pegylated FeS nanoparticles as carrier for drug delivery and the killing effect of FeS-PEG loaded nanoparticles on tumor cells

目的探讨具有良好生物相容性的多功能纳米材料FeS-PEG的载药性能,以及其在载带抗肿瘤小分子药物盐酸阿霉素(DOX)后DOX对肿瘤细胞4T1细胞增殖、入胞、凋亡的影响。方法采用高温合成法合成纳米材料FeS,经层层交联修饰FeS得到FeS-PEG;分析FeS-PEG的细胞毒性、载药性能并进行载药入胞和细胞凋亡检测。结果FeS-PEG纳米材料对抗肿瘤药物DOX的载药率为134%,载药后在pH=7.4的环境下释药7.13%,pH=6释药10.94%,pH=5释药24.53%。并且FeS-PEG载药后可将DOX药物滞留于细胞质中;游离DOX培养细胞促进细胞凋亡比例为(5.1±0.72)%,而FeS-PEG载药后可促进细胞凋亡比例(31.28±2.28)%。结论FeS-PEG纳米材料可载带小分子药物,改变小分子药物在细胞内的停留部位,将小分子药物滞留于细胞质中,另外,该纳米材料载带药物后可明显促进细胞凋亡,从而达到增强药物对肿瘤细胞的持久杀伤作用,在药物载带输送方面具有很大应用前景。

Objective To explore the drug loading properties of multi-functional nanometer material pegylated FeS(FeS-PEG)nanoparticles with good biocompatibility,and the effect of doxorubicin(DOX)on the proliferation,endocytosis and apoptosis of tumor cell 4T1 after anti-tumor drug DOX was carried by FeS-PEG.Methods Nanostructured FeS was synthesized by high temperature synthesis,and FeS-PEG was obtained by crosslinking modification of FeS layer by layer.The cytotoxicity and drug loading properties of FeS-PEG were analyzed,and the endocytosis of the loaded drugs and apoptosis were detected.Results The drug loading rate of the anti-tumor drug DOX loaded by FeS-PEG nanomaterials was 134%.The loaded drugs were released by 7.13%if pH=7.4,by 10.94%if pH=6,by 24.53%if pH=5.The drugs loaded by FeS-PEG could retain DOX in the cytoplasm.The percentage of apoptosis promoted by free DOX culture was(5.1±0.72)%,while that by the drugs loaded with FeS-PEG was(31.28±2.28)%.Conclusion FeS-PEG nanomaterials can carry small molecule drugs,change the retention site of small molecule drugs in cells,and retain small molecule drugs in cytoplasm.In addition,the nanomaterials can obviously promote cell apoptosis after drug loading,so as to enhance the long-term killing effect of drugs on tumor cells,which has a great application prospect in drug delivery.