PMLA-PEG-TAT纳米接枝物的合成和生物活性研究  

TAT-conjugated poly(β-malic acid)-poly(ethylene glycol)nanoconjugate:synthesis and biological evaluation

作　　者：郭松岩[1] 崔明凤 周青[1] 乔友备[1] 吴娟[2] 桑广泽 王玉琨[1] 吴红[1] 

机构地区：[1]第四军医大学药学院药物分析学教研室,西安710032 [2]第四军医大学西京医院妇产科,西安710032

出　　处：《西北药学杂志》2015年第2期176-181,共6页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81271687)

摘　　要：目的合成药物载体聚苹果酸(PMLA),制备纳米接枝物PMLA-Hyd-PEG5000/PEG2000-TAT/Doxorubicin(DOX),研究PEG对穿膜肽的保护作用及入胞特性。方法以L-天冬氨酸为原料合成PMLA,将不同相对分子质量聚乙二醇(PEG5000)和PEG2000-TAT分别通过腙键和酰胺键与PMLA相连。阿霉素(DOX)作为模型药物,通过酰胺键与PMLA相连。采用Hela细胞研究纳米接枝物的细胞毒性和细胞内摄作用。结果成功制备了药物载体PMLA和纳米接枝物PMLA-Hyd-PEG5000/PEG2000-TAT/DOX,筛选出当TAT含量为0.3%(TAT与PMLA的摩尔比,mol/mol)可发挥很好地穿膜入胞作用,PEG5000含量为3.2%(PEG与PMLA的摩尔比,mol/mol,下同)时对0.3%TAT有很好的保护作用,激光共聚焦实验(CLSM)验证了MTT实验结果。结论一定量PEG5000对TAT有很好的保护作用,为后续去保护后,TAT发挥高效入胞作用提供前期研究基础。Objective The drug carrier of poly（β-malic acid）（PMLA）was synthesized to afford a novel nanoconjugate named poly（β-malic acid）-hydrazone bond-poly（ethylene glycol）5000（PEG5000）/PEG2000-TAT peptide/doxorubicin（DOX）for active tumor targeting.Methods The drug carrier PMLA was synthesized by L-aspartic acid.Different molecular weight PEGs were conjugated with PMLA by hydrazone bond and amide bond,respectively.The cytotoxicity and the cellular uptake assay were conducted by Hela cells.Result PMLA and nanoconjugate PMLA-Hyd-PEG5000/PEG2000-TAT/DOX were successfully prepared.The appropriate content of PEG（3.2%,mol/mol）was screened for hiding of TAT（0.3%,mol/mol）by cytotoxicity assay.The CLSM assay confirmed the result.Conclusion The TAT peptide was effectively protected by the appropriate content of PEG5000.This study provided an early foundation for the TAT peptide efficiently exerted cellular uptaking when the PEG5000 was taken off.

关 键 词：TAT 聚乙二醇 聚苹果酸 纳米接枝物 

分 类 号：R914[医药卫生—药物化学]