三氧化二砷氧化还原性纳米递药系统的生物学评价

Biological evaluation of arsenic trioxide redox nano drug delivery system

目的本研究基于三氧化二砷氧化还原性纳米递药系统观察其在人源性肝癌细胞(HepG2细胞)的摄取情况以及在裸鼠肝癌模型中的抗肿瘤效果。方法采用激光共聚焦观察三氧化二砷氧化还原性纳米递药系统在HepG2细胞的摄取情况,构建BALB/c裸鼠肝癌模型并进行模型鼠肿瘤体积和体质量监测、存活率观察、肿瘤切片实验等实验研究其抑制肝癌生长的效果。结果HepG2细胞对氧化还原性纳米载体MSN-SS-PEG具有较好的摄取,生理盐水组、As2O3、MSN-SS-NH_(2)@As_(2)O_(3)组、MSN-SS-PEG@As_(2)O_(3)组的肿瘤体积分别为(1508.96±452.59)mm^(3)、(1293.29±163.89)mm^(3)、(890.58±178.57)mm^(3)、(488.39±279.43)mm^(3),存活率分别为(20.2±0.84)d、(22.8±0.84)d、(22.8±2.12)d、(26.0±1.00)d。与As2O3组比较,MSN-SS-NH_(2)@As_(2)O_(3)和MSN-SS-PEG@As_(2)O_(3)组的细胞凋亡或坏死面积逐渐增大。结论生物学评价证明经过修饰后的纳米给药系统能在一定程度上促进纳米递药系统入胞增加其抗肿瘤效果,体内药效学进一步表明所构建的纳米给药系统提高了裸鼠的生存时间,具有较好的肿瘤治疗效果。

Objective This paper aims to study the uptake of arsenic trioxide redox nano drug delivery system in HepG2 cells and its role in nude mouse liver cancer model.Methods The uptake of arsenic trioxide redox nano drug delivery system in HepG2 cells was studied by laser confocal method.By constructing BALB/c nude mice liver cancer model,monitoring the tumor volume and weight of model mice,and observing the survival rate of model mice and tumor section experiment,the experiment of inhibiting the growth of liver cancer was carried out.Results Good uptake of the redox nano carrier MSN-SS-PEG was observed in HepG2 cells.The tumor volume of normal saline group,As_(2)O_(3)group,MSN-SS-NH_(2)@As_(2)O_(3)group,and MSN-SS-PEG@As_(2)O_(3)group was(1508.96±452.59)mm^(3),(1293.29±163.89)mm^(3),(890.58±178.57)mm^(3),and(488.39±279.43)mm^(3),respectively;their survival rates were respectively(20.2±0.84)d,(22.8±0.84)d,(22.8±2.12)d,and(26.00±1.00)d.Compared with As_(2)O_(3)group,the apoptotic or necrotic area of tumor cells increased gradually in MSN-SS-NH_(2)@As_(2)O_(3)group and MSN-SS-PEG@As_2O_(3)group.Conclusion Biological evaluation showed that the modified nano drug delivery system can promote the entry of nano drug delivery system into cells and increase its antitumor effect to a certain extent.In vivo pharmacodynamics further showed that the constructed nano delivery system improves the survival time of nude mice and has good tumor therapeutic effect.