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Influence of Lysine and TRITC Conjugation on the Size and Structure of Dextran Nanoconjugates with Potential for Biomolecule Delivery to Neurons
ACS Applied Bio Materials ( IF 4.7 ) Pub Date : 2021-08-23 , DOI: 10.1021/acsabm.1c00544
Darya Zeini 1, 2 , Joel C Glover 2, 3 , Kenneth D Knudsen 4 , Bo Nyström 1
Affiliation  

As a potent nonviral system for biomolecular delivery to neurons via their axons, we have studied molecular characteristics of lysinated fluorescent dextran nanoconjugates with degrees of conjugation of 0.54–15.2 mol lysine and 0.25–7.27 mol tetramethyl rhodamine isothiocyanate (TRITC) per mol dextran. We studied the influence of conjugation with lysine and TRITC on the size and structure of different molecular weight dextrans and their mobility within axons. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) experiments revealed significant differences in the size and structure of unmodified and modified dextrans. Unexpectedly, lower-molecular-weight conjugated dextrans exhibited higher molecular volumes, which we propose is due to fewer intramolecular interactions than in higher-molecular-weight conjugated dextrans. Assessment of retrograde and anterograde movement of lysine- and TRITC-conjugated dextrans in axons in the lumbar spinal cord of chicken embryos showed that lower-molecular-weight dextrans translocate more efficiently than higher-molecular-weight dextrans, despite having larger molecular volumes. This comparative characterization of different molecular weight dextrans will help define optimal features for intracellular delivery.

中文翻译:

赖氨酸和 TRITC 共轭对葡聚糖纳米共轭的大小和结构的影响,具有向神经元传递生物分子的潜力

作为通过轴突向神经元传递生物分子的有效非病毒系统,我们研究了每 mol 葡聚糖共轭度为 0.54-15.2 mol 赖氨酸和 0.25-7.27 mol 四甲基罗丹明异硫氰酸酯 (TRITC) 的裂解荧光葡聚糖纳米偶联物的分子特征。我们研究了与赖氨酸和 TRITC 共轭对不同分子量葡聚糖的大小和结构及其在轴突内的迁移率的影响。动态光散射 (DLS) 和小角中子散射 (SANS) 实验揭示了未改性和改性葡聚糖的大小和结构存在显着差异。出乎意料的是,低分子量共轭葡聚糖表现出更高的分子体积,我们认为这是由于分子内相互作用比高分子量共轭葡聚糖少。对鸡胚胎腰脊髓轴突中赖氨酸和 TRITC 共轭葡聚糖的逆行和顺行运动的评估表明,尽管分子体积较大,但低分子量葡聚糖比高分子量葡聚糖更有效地易位。这种不同分子量葡聚糖的比较表征将有助于确定细胞内递送的最佳特征。
更新日期:2021-09-20
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