TMZ@ZIF-8纳米粒的制备、表征及体内外抗肿瘤研究

TMZ@ZIF-8 nanoparticles:preparation,characterization,and in vivo and in vitro anti-tumor studies

目的制备沸石咪唑骨架(ZIF)-8纳米粒(NPs)负载替莫唑胺(TMZ)(简称TMZ@ZIF-8 NPs)药物递送系统,以增加药物在病灶的富集和抗脑胶质瘤效果。方法采用室温溶液反应法制备ZIF-8 NPs后,再采用浸渍法制备TMZ@ZIF-8 NPs药物递送系统。进行透射电镜、激光粒度及傅里叶变换红外光谱等表征和溶出实验,并进行体外及体内抗肿瘤活性实验。结果TMZ@ZIF-8 NPs制备成功,粒径为(126.23±7.92)nm,载药率为(28.79±1.26)%,72 h累积溶出速率为(72.36±3.62)%。体外抗肿瘤活性实验结果显示,ZIF-8 NPs的相对细胞存活率一直保持在90%以上;与游离的TMZ相比,TMZ@ZIF-8 NPs对C6细胞的生长、增殖表现出更优的抑制作用、更高的被摄取能力和更好的促凋亡效果。体内抗肿瘤活性实验结果显示,ZIF-8 NPs在大鼠脑部不富集,TMZ在脑部富集效果并不显著,而TMZ@ZIF-8 NPs在脑部富集效果显著。结论ZIF-8 NPs可有效负载TMZ,制备成功的TMZ@ZIF-8可提高TMZ摄取能力及抗脑胶质瘤效果。

OBJECTIVE To prepare zeolite imidazole framework(ZIF)-8 nanoparticles(NPs)loaded with temozolomide(TMZ)(abbreviated as TMZ@ZIF-8 NPs)drug delivery system,thus increasing drug enrichment and anti-glioma effects in lesions.METHODS After preparing ZIF-8 NPs using the room temperature solution reaction method,the impregnation method was used to prepare TMZ@ZIF-8 NPs drug delivery system.Characterization was carried out using transmission electron microscopy,laser particle size,and Fourier transform infrared spectroscopy,and dissolution and anti-tumor activity experiments in vitro and in vivo were conducted.RESULTS TMZ@ZIF-8 NPs were successfully prepared with the particle size of(126.23±7.92)nm,drug loading amount of(28.79±1.26)%,and 72 h cumulative dissolution rate of(72.36±3.62)%.The results of in vitro anti-tumor activity experiments showed that the relative cell survival rate of ZIF-8 NPs remained above 90%;the prepared TMZ@ZIF-8 NPs delivery system exhibited superior inhibition,higher uptake capacity,and better promoting apoptosis effects on the growth and proliferation of C6 cells as compared with the free TMZ.The results of in vivo anti-tumor activity experiments showed that ZIF-8 NPs were not enriched in the brain of rats,and the enrichment effect of TMZ in the brain was not significant,while TMZ@ZIF-8 NPs had a significant enrichment effect in the brain.CONCLUSIONS ZIF-8 NPs can effectively load TMZ,and successfully prepared TMZ@ZIF-8 NPs can improve TMZ uptake ability and anti-glioma effect.