Synthesis of bisethylnorspermine lipid prodrug as gene delivery vector targeting polyamine metabolism in breast cancer.
Synthesis of bisethylnorspermine lipid prodrug as gene delivery vector targeting polyamine metabolism in breast cancer.
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DOI：
10.1021/mp300001m
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发表时间：
2012-06-04
影响因子：
4.9
通讯作者：
Oupický D
中科院分区：
文献类型：
--
作者：
Dong Y;Zhu Y;Li J;Zhou QH;Wu C;Oupický D
非病毒基因传递载体的发展继续受到低转染活性和毒性的阻碍。在这里，我们建议开发一种脂质前药的基础上多胺类似物bisethylnorspermine（BSP），可以双重功能的基因传递载体，细胞内降解后，作为活性抗癌剂靶向失调的多胺代谢。我们合成了一个前体药物的BSP（LS-BSP），能够细胞内释放的BSP使用硫解敏感的二硫代苄基氨基甲酸酯连接。与不可降解的对照L-BSP相比，LS-BSP的生物降解性有助于降低毒性。BSP对人乳腺癌细胞中肿瘤坏死因子相关凋亡诱导配体（TRAIL）的细胞毒活性有很强的协同增强作用。与BSP相比，观察到LS-BSP的TRAIL活性增强降低。LS-BSP与质粒DNA形成复合物，介导的转染活性与DOTAP和L-BSP相当。我们的研究结果表明，BSP为基础的载体是有前途的候选人组合药物/基因传递。
Progress in the development of nonviral gene delivery vectors continues to be hampered by low transfection activity and toxicity. Here we proposed to develop a lipid prodrug based on a polyamine analogue bisethylnorspermine (BSP) that can function dually as gene delivery vector and, after intracellular degradation, as active anticancer agent targeting dysregulated polyamine metabolism. We synthesized a prodrug of BSP (LS-BSP) capable of intracellular release of BSP using thiolytically sensitive dithiobenzyl carbamate linker. Biodegradability of LS-BSP contributed to decreased toxicity compared with nondegradable control L-BSP. BSP showed a strong synergistic enhancement of cytotoxic activity of TNF-related apoptosis-inducing ligand (TRAIL) in human breast cancer cells. Decreased enhancement of TRAIL activity was observed for LS-BSP when compared with BSP. LS-BSP formed complexes with plasmid DNA and mediated transfection activity comparable to DOTAP and L-BSP. Our results show that BSP-based vectors are promising candidates for combination drug/gene delivery.
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DOI：
10.1016/0006-291x(89)91082-6
发表时间：
1989-11-30
影响因子：
3.1
作者：
CELANO, P;BERCHTOLD, CM;CASERO, RA
通讯作者：
CASERO, RA
影响因子：
7.3
作者：
Cogan, PS;Koch, TH
通讯作者：
Koch, TH
影响因子：
7.3
作者：
BERGERON, RJ;NEIMS, AH;INGENO, MJ
通讯作者：
INGENO, MJ
影响因子：
3.6
作者：
Huang, Y;Pledgie, A;Davidson, NE
通讯作者：
Davidson, NE
MDR和非MDR细胞中对pluron子的差异代谢反应：耐药性癌症化学敏化的新途径。
影响因子：
10.8
作者：
Alakhova, Daria Yu.;Rapoport, Nataliya Y.;Batrakova, Elena V.;Timoshin, Alexander A.;Li, Shu;Nicholls, David;Alakhov, Valery Yu.;Kabanov, Alexander V.
通讯作者：
Kabanov, Alexander V.