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Macrocyclic polyamine [12]aneN3 modified triphenylamine-pyrazine derivatives as efficient non-viral gene vectors with AIE and two-photon imaging properties.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-05-06 , DOI: 10.1039/d0tb00321b Le-Le Ma 1 , Ming-Xuan Liu 1 , Xu-Ying Liu 1 , Wan Sun 1 , Zhong-Lin Lu 1 , Yong-Guang Gao 2 , Lan He 3
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-05-06 , DOI: 10.1039/d0tb00321b Le-Le Ma 1 , Ming-Xuan Liu 1 , Xu-Ying Liu 1 , Wan Sun 1 , Zhong-Lin Lu 1 , Yong-Guang Gao 2 , Lan He 3
Affiliation
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With the aim to develop a novel multifunctional gene delivery system that may overcome the common barriers of gene transfection, near-infrared fluorescent triphenylamine-pyrazine was modified with a DNA condensing triazole-[12]aneN3 moiety through different length alkyl ester linkages to afford three new non-viral gene vectors, TDM-A/B/C. All compounds showed prominent solvatochromic fluorescence (Stokes shift of up to 383 nm) and two-photon absorption properties (σ2P to 101 GM), and exhibited strong aggregation-induced emission (AIE). Gel electrophoresis demonstrated that plasmid DNA was completely condensed at a concentration of 10 μM (TDM-A), 14 μM (TDM-B) and 16 μM (TDM-C), and released in esterase and acidic environment. SEM demonstrated that the three compounds were able to self-assemble and co-aggregate with DNA to form regular nanoparticles. Experiments demonstrated that TDM-A/B/C was able to integrate with DNA through electrostatic interactions and supramolecular stacking, and the short alkyl linkage favored the strong interaction with DNA. Among the three compounds, TDM-B showed the best luciferase and GFP transfection activities in the presence of DOPE, which were 156% and 310% higher than those of Lipo2000, respectively. The transfection process of DNA was clearly traced through one- and two-photon fluorescence microscopy imaging. Cellular uptake inhibition assay indicated that the DNA complex entered the cell mainly via clathrin-independent endocytosis. Furthermore, the in vivo transfection experiments of TDM-B/DOPE were successfully implemented in zebra fish embryos, and the GFP gene expression level was superior to that of Lipo2000 (200%). Finally, this study clearly unraveled that the length of the alkyl linkage affected the DNA condensation and transfection activity, which can serve as a base for the future rational design of non-viral gene vectors.
中文翻译：
大环多胺[12] aneN3修饰的三苯胺-吡嗪衍生物作为具有AIE和双光子成像特性的有效非病毒基因载体。
为了开发一种可以克服基因转染常见障碍的新型多功能基因递送系统，将近红外荧光三苯胺-吡嗪通过DNA缩合三唑-[12] aneN3部分的DNA通过不同长度的烷基酯键进行修饰，得到三个新的非病毒基因载体TDM-A / B / C。所有化合物均显示出显着的溶剂变色荧光（斯托克斯位移最大383 nm）和双光子吸收特性（σ2P至101 GM），并表现出强聚集诱导发射（AIE）。凝胶电泳显示质粒DNA在10μM（TDM-A），14μM（TDM-B）和16μM（TDM-C）的浓度下完全浓缩，并在酯酶和酸性环境中释放。SEM显示这三种化合物能够自组装并与DNA共聚集形成规则的纳米粒子。实验表明，TDM-A / B / C能够通过静电相互作用和超分子堆积与DNA整合，而短烷基键有利于与DNA的强相互作用。在这三种化合物中，在DOPE存在下，TDM-B表现出最好的荧光素酶和GFP转染活性，分别比Lipo2000高156％和310％。DNA的转染过程通过一光子和二光子荧光显微镜成像清晰地追踪到。细胞摄取抑制试验表明，DNA复合物主要通过网格蛋白非依赖性内吞作用进入细胞。此外，在斑马鱼胚胎中成功进行了TDM-B / DOPE的体内转染实验，其GFP基因表达水平优于Lipo2000（200％）。最后，这项研究清楚地揭示了烷基键的长度会影响DNA的缩合和转染活性，这可以为将来非病毒基因载体的合理设计奠定基础。
更新日期：2020-03-11
中文翻译：
大环多胺[12] aneN3修饰的三苯胺-吡嗪衍生物作为具有AIE和双光子成像特性的有效非病毒基因载体。
为了开发一种可以克服基因转染常见障碍的新型多功能基因递送系统，将近红外荧光三苯胺-吡嗪通过DNA缩合三唑-[12] aneN3部分的DNA通过不同长度的烷基酯键进行修饰，得到三个新的非病毒基因载体TDM-A / B / C。所有化合物均显示出显着的溶剂变色荧光（斯托克斯位移最大383 nm）和双光子吸收特性（σ2P至101 GM），并表现出强聚集诱导发射（AIE）。凝胶电泳显示质粒DNA在10μM（TDM-A），14μM（TDM-B）和16μM（TDM-C）的浓度下完全浓缩，并在酯酶和酸性环境中释放。SEM显示这三种化合物能够自组装并与DNA共聚集形成规则的纳米粒子。实验表明，TDM-A / B / C能够通过静电相互作用和超分子堆积与DNA整合，而短烷基键有利于与DNA的强相互作用。在这三种化合物中，在DOPE存在下，TDM-B表现出最好的荧光素酶和GFP转染活性，分别比Lipo2000高156％和310％。DNA的转染过程通过一光子和二光子荧光显微镜成像清晰地追踪到。细胞摄取抑制试验表明，DNA复合物主要通过网格蛋白非依赖性内吞作用进入细胞。此外，在斑马鱼胚胎中成功进行了TDM-B / DOPE的体内转染实验，其GFP基因表达水平优于Lipo2000（200％）。最后，这项研究清楚地揭示了烷基键的长度会影响DNA的缩合和转染活性，这可以为将来非病毒基因载体的合理设计奠定基础。
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