Serrano Christopher M, Freeman Ronit, Godbe Jacqueline, Lewis Jacob A, Stupp Samuel I
Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, Illinois 60208, USA.
Simpson Querrey Institute, Northwestern University, 303 East Superior Street, Chicago, Illinois 60611, USA.
ACS Appl Bio Mater. 2019 Jul 15;2(7):2955-2963. doi: 10.1021/acsabm.9b00310. Epub 2019 Jun 18.
The single stranded DNA oligonucleotides known as aptamers have the capacity to bind proteins and other molecules and offer great therapeutic potential. Further work is required to optimize their function and to diminish their susceptibility to nuclease degradation. We report here on the synthesis and supramolecular self-assembly of DNA-peptide amphiphiles that form high aspect ratio nanofibers and display aptamers for platelet-derived growth factor. The nanofibers were found to bind the growth factor with an affinity that was fivefold greater than the free aptamer. We also observed that the aptamer displayed by the supramolecular nanostructures was eight times more nuclease resistant than free aptamer. In order to highlight the therapeutic potential of these supramolecular systems, we demonstrated the improved inhibition of proliferation when the growth factor was bound to aptamers displayed by the nanofibers.
被称为适配体的单链DNA寡核苷酸具有结合蛋白质和其他分子的能力,并具有巨大的治疗潜力。需要进一步开展工作来优化其功能,并降低它们对核酸酶降解的敏感性。我们在此报告了DNA-肽两亲分子的合成及超分子自组装,这些分子形成了高纵横比的纳米纤维,并展示了针对血小板衍生生长因子的适配体。研究发现,这些纳米纤维与生长因子的结合亲和力比游离适配体高五倍。我们还观察到,超分子纳米结构展示的适配体对核酸酶的抗性比游离适配体高八倍。为了突出这些超分子系统的治疗潜力,我们证明了当生长因子与纳米纤维展示的适配体结合时,对细胞增殖的抑制作用有所增强。