聚合物修饰的蓖麻毒蛋白A链在荷瘤大鼠体内分布的研究

Study on Biodistribution of Ricin A Chain Modified by Polymers in Rats Bearing Tumors

目的研究两种不同相对分子质量的单甲氧聚乙二醇(monomethoxypolyethyleneglycol,mPEG)与蓖麻毒蛋白A链(ricinAchain,RTA)偶联后在荷瘤大鼠体内分布情况,探讨聚合物修饰的RTA靶向治疗肿瘤的可能性。方法荷瘤大鼠动物模型分3组,分别尾静脉注射125I-RTA,125I-RTA-mPEG-MAL和125I-RTA-mPEG-OPSS后,在不同时间点分批处死大鼠,行组织分布测定,并相互比较。结果RTA-mPEG偶联物的生物半衰期较RTA有明显延长,且随时间的延长RTA-mPEG偶联物的瘤/非瘤组织的放射性比值与RTA比显著增大。在肝、脾脏组织,注射后1h测得RTA摄取率大于RTA-mPEG偶联物。结论通过聚乙二醇的修饰,使RTA生物半衰期大大延长,且修饰后能避免肝脏、脾脏的摄取,并靶向到肿瘤组织。

OBJECTIVE To study the biodistribution of ricin A-chain （RTA） and mPEG modified RTA in rats beating tumors and discuss the feasibility of tumor targeting treatment using RTA modified by polymer. METHODS Rats bearing tumors were divided in 3 groups, injected ^125I-RTA, ^125I-RTA-mPEG-MAL and ^125I-RTA-mPEG-OPSS through tail venous and sacrificed at different time intervals. Then their biodistributions were assessed and compared. RESULTS The biologic half-lives of RTA-mPEG conjugates were prolonged significantly compared with RTA. The ratios of radioactivity of T/TN for ^125I-labeled PEG-RTAs appeared a clear step-up tendency as a function of time. And the take-ups of liver and spleen for ^125I-RTA were greater than those for PEG-RTAs after lh administration. CONCLUSION The biologic half-life of RTA can be prolonged through PEGylation. And RTA modified by PEG can avoid the take-ups of liver and spleen,at the same time accumulate in tumor tissues.