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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
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摘要 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.
出处 《中国药学杂志》 CAS CSCD 北大核心 2007年第2期113-115,146,共4页 Chinese Pharmaceutical Journal
基金 国家自然科学基金资助项目(30271552)
关键词 聚乙二醇 蓖麻毒蛋白A链 体内分布 polyethylene glycol ricin A chain biodistribution
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参考文献7

  • 1葛利萍,詹金彪.蓖麻毒素在细胞内的运输和转运途径研究进展[J].浙江大学学报(医学版),2003,32(6):538-542. 被引量:5
  • 2HIROSHI M,LEN W S,YOICHI M.Conjugates of anticancer agents and polymers:advantages of macromolecular therapeutics in Vivo[J].Bioconjug Chem,1992,3:351-362.
  • 3黎维勇,方凯,宋波,郭文韬,陈华庭.聚乙二醇修饰的蓖麻毒蛋白A链免疫原性与毒性的研究[J].中国药学杂志,2005,40(13):1026-1028. 被引量:5
  • 4LEE K C,MOON S C,PARK M O,et al.Isolation,characterization and stability of positional isomers of mono-PEGylated salmon calcitonins[J].Pharm Res,1999,16:813-818
  • 5BLAKEY D C,THORPE P E.Effect of chemical deglycosylation on the in vivo fate of ricin A chain[J].Cancer Drug Deliv,1986,3:189-196.
  • 6BOURRIE B J P,CASELLAS P,BLYTHMAN H E.Study of the plasma clearance of antibody-ricin A chain immunotoxins[J].Eur J Biochem,1986,155:1-10.
  • 7BLAKEY D C,WATSON G J,KNOWLES P P,et al.Effect of chemical deglycosylation of ricin A chain on the in vivo fate and cytotoxic activity of an immunotoxin composed of ricin A chain and anti-Thy 1.1 antibody[J].Cancer Res,1987,47:947-952.

二级参考文献6

  • 1詹金彪 周佩珩.Purification and biological activitis of ricin [J].Journal of Zhejiang Medical University(浙江医科大学学报),1990,19(6):252-254.
  • 2Esslinger HU, Haas S, Maurer R, et al. Pharmacodynamic and safty results of PEG-hirudin in healthy volunteers[ J]. Thromb Haemost,1997,77:911.
  • 3Tsutsumi Y, Kihira T, Tsunoda S, et al. Molecular design of hybrid tumor necrosis factor alfa with polyethylene glycol increases its anti-tumour potency[J]. Br J Cancer, 1995,71:963.
  • 4Thomas T, Steven S. Purification and physicochemical properties of ricins and agglutinins from ricinus communis [ J ] . Eur J Biochem,1980,105:453.
  • 5穆援越 汪家政 范明.免疫印迹[A].汪家政,范明.蛋白质技术手册[M].北京:科学出版社,2000.166-180.
  • 6Roberts MJ, Bentley MD, Harris JM. Chemistry for peptide and protein PEGylation[J]. Adv Drug Deliv Rev,2002,54:459.

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