可断裂PEG与RGD共修饰脂质体的制备及其初步评价

摘要

Objective To prepare the cleavable PEG and RGD co-modified liposome for tumor targeting.Methods Liposomes were prepared by film-ultrasonic method.The particle size,Zeta potential and stability in FBS were evaluated.Cellular uptake by HepG2 cell was explored.MTT assay was used to evaluate the cytotoxicity of blank liposomes. Results The particle diameter of C/RGD-LP was (104.8 ±5.5 )nm with the Zeta potential of (-4.45 ±1.75 )mV.The cellular uptake of C/RGD-LP increased 2.8 times after Cys was added.The C/RGD-LP showed little cytotoxicity to HepG2 cell.Conclusion Cleavable PEG and RGD co-modified liposomes were easy to prepare and has a special application value for targeting tumor.%目的：制备氧化-还原敏感的可断裂PEG（聚乙二醇，polyethylene glycol）与RGD（精氨酸-甘氨酸-天冬氨酸，Arg-Gly-Asp）共修饰脂质体（C/RGD-LP），并对其体外性质进行评价。方法采用薄膜分散法制备可断裂PEG与RGD共修饰脂质体，测定脂质体的粒径、电位以及血清稳定性。采用流式观察肝癌HepG2细胞在PEG断裂前后对脂质体摄取效率的变化。MTT法检测该脂质体对细胞的毒性。结果 C/RGD-LP的粒径为（104.8±5.5）nm，电位为（-4.45±1.75）mV，在血清中有良好的稳定性。加入还原剂半胱氨酸后，HepG2细胞对PEG断裂后的脂质体摄取效率为断裂前的2.8倍，差异有统计学意义（P＜0.01）；细胞摄取实验结果显示：加入还原剂半胱氨酸后，PEG断裂后细胞的荧光强度显著强于未加入Cys组和无RGD修饰普通脂质体组（P＜0.01）。MTT实验结果表明：C/RGD-LP无明显细胞毒性。结论可断裂PEG与RGD共修饰脂质体制备方法简单，具有良好的稳定性，PEG能够有效屏蔽RGD肽，是一种潜在的肿瘤靶向给药系统。