聚乙二醇修饰对羟喜树碱隐形纳米囊泡的肿瘤靶向和抑瘤作用的影响

Tumor targeting effect and anti-tumor activity of hydroxycamptothecin loaded stealth niosomes with different polyethylene glycol chain length

目的探讨聚乙二醇相对分子质量对载羟喜树碱(HCPT)的聚乙二醇化聚十六烷基氰基丙烯酸酯纳米囊泡(PEG-PHDCA)在S180肉瘤小鼠体内的肿瘤靶向性及抗肿瘤作用的影响。方法选用司盘60和PEG-PHDCA为载体材料,制备HCPT的PEG-PHDCA隐形纳米囊泡,进行S180肉瘤小鼠瘤内药动学试验和抑瘤试验。结果PEG相对分子质量为2 000、5 000、10 000的PEG-PHDCA纳米囊泡在S180肉瘤小鼠肿瘤中125I-HCPT的AUC分别为HCPT的9.21、13.82、9.48倍;对S180肉瘤小鼠抑瘤率分别为88%、97.1%、80.8%,普通纳米粒PHDCA组抑瘤率为41.8,而原药组抑瘤率仅为17.3%。结论PEG修饰纳米囊泡明显优于原药和未经PEG修饰纳米囊泡,PEG相对分子质量为5 000,粒径为80 nm左右时,载HCPT的隐形纳米囊泡具有最佳肿瘤靶向作用。

AIM To investigate the tumor targeting effect and anti-tumor activity of hydroxycamptothecin （HCPT） loaded poly （methoxy-polyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate） （PEG-PHDCA） niosomes with different polyethylene glycol （PEG） chain length. METHODS Stealth PEG-PHDCA niosomes were prepared with span60 and PEG-PHDCA acting as drug carrier. S180 tumor bearing mice were used for biodistribution test and anti-tumor test. RESULTS Niosomes with PEG chain length of 2 000, 5 000, 10 000 showed an obvious tumor targeting effect, with AUC in tumor increasing by 9.21, 13.82 and 9.48-fold, respectively, compared with HCPT. The tumor inhibition rate of niosomes with PEG chain length of 5 000, 2 000, 10 000 were 88 %, 97.1%, 80.8 %, respectively, while HCPT had only 17.3 % inhibition rate. CONCLUSION PEG-PHDCA niosomes have a better anti-tumor effect than HCPT and PHDCA niosomes. Under this experimental conditions, PEG-PHDCA niosomes with PEG chain length of 5 000 and particle size of 80 nm have the most significant tumor targeting effect.