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Alkyl-Modified Oligonucleotides as Intercalating Vehicles for Doxorubicin Uptake via Albumin Binding
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2018-01-08 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00805
Laura Purdie 1 , Cameron Alexander 1 , Sebastian G. Spain 2 , Johannes P. Magnusson 1
Affiliation  

DNA-based drug delivery vehicles have displayed promise for the delivery of intercalating drugs. Here, we demonstrate that oligonucleotides modified with an alkyl chain can bind to human serum albumin, mimicking the natural binding of fatty acids. These alkyl-DNA–albumin complexes display excellent serum stability and are capable of strongly binding doxorubicin. Complexes are internalized by cells in vitro, trafficking to the mitochondria, and are capable of delivering doxorubicin with excellent efficiency resulting in cell death. However, the cellular localization of the delivered doxorubicin, and ultimately the complex efficacy, is dependent on the nature of the linker between the alkyl group and the oligonucleotide.

中文翻译:

烷基修饰的寡核苷酸作为通过白蛋白结合吸收阿霉素的插入载体

基于DNA的药物递送工具已显示出对嵌入药物进行递送的希望。在这里,我们证明了用烷基链修饰的寡核苷酸可以与人血清白蛋白结合,模仿脂肪酸的天然结合。这些烷基-DNA-白蛋白复合物具有出色的血清稳定性,能够与阿霉素强结合。复合物在体外被细胞内化,运输到线粒体,并且能够以优异的效率递送阿霉素,从而导致细胞死亡。然而,所递送的阿霉素的细胞定位以及最终的复杂功效取决于烷基和寡核苷酸之间的接头的性质。
更新日期:2018-01-08
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