Effective delivery of luminescent probes for cell imaging requires both cell membrane permeation and directing to discrete target organelles. Combined, these requirements can present a significant challenge for metal complex luminophores, that have excellent properties as imaging probes but typically show poor membrane permeability. Here, we report on highly luminescent Ruthenium polypyridyl complexes based on the parent; [Ru(dpp)₂(x-ATAP)](PF₆)₂ structure, where dpp is 4,7-diphenyl-1,10-phenanthroline and x-ATAP is 5-amino-1,10-phenanthroline with pendant alkyl-acetylthio chains of varying length; where x is 6; 5-Amido-1,10-phenanthroline-(6-acetylthio-hexanyl). 8; 5-Amido-1,10-phenanthroline-(8-acetylthio-octanyl). 11; 5-Amido-1,10-phenanthroline-(11-acetylthio-undecanyl); and 16; 5-Amido-1,10-phenanthroline-(16-acetylthio-hexadecanyl). Soluble in organic media, the alkyl-acetylthiolated complexes form nanoaggregates of low polydispersity in aqueous solution. From dynamic light scattering the nanoaggregate diameter was measured as 189 nm and 135 nm for 5 × 10⁻⁶ M aqueous solutions of [Ru(dpp)₂(N∧N)](PF₆)₂ with the hexadecanoyl and hexanyl tails respectivly. The nanoaggregate exhibited dual exponential emission decays with kinetics that matched closely those of the [Ru(dpp)₂(16-ATAP)]²⁺ incorporated into the membrane of a DPPC liposome. Cell permeability and distribution of [Ru(dpp)₂(11-ATAP)]²⁺ or [Ru(dpp)₂(16-ATAP)]²⁺ were evaluated in detail in live HeLa and CHO cell lines and it was found from aqueous media, that the nanoaggregate complexes spontaneously cross the membrane of mammalian cells. This process seems, on the basis of temperature dependent studies to be activated. Fluorescence imaging of live cells reveal that the complexes localize highly specifically within organelles and that organelle localization changes dramatically in switching the pendent alkyl chains from C16 to C11 as well as on cell line identity. Our data suggests that building metal complexes capable of self-assembling into nano-dimensional vesicles in this way may be a useful means of promoting cell membrane permeability and driving selective targeting that is facile and relatively low cost compared to use of biomolecular vectors.

有效递送用于细胞成像的发光探针既需要细胞膜渗透，又需要引导至离散的靶细胞器。结合起来，这些要求对金属络合物发光体提出了巨大的挑战，金属络合物发光体具有出色的成像探针性能，但通常膜渗透性较差。在这里，我们报道了基于母体的高发光钌多吡啶基配合物。[Ru（dpp）₂（x-ATAP）] [PF ₆）₂结构，其中dpp是4，7-二苯基-1，10-菲咯啉，x-ATAP是5-氨基-1，10-菲咯啉，具有不同长度的烷基-乙酰硫基侧链。其中x是6; 5-氨基-1,10-菲咯啉-（6-乙酰硫基-己基）。8; 5-氨基-1,10-菲咯啉-（8-乙酰硫基-辛基）。11; 5-氨基-1,10-菲咯啉-（11-乙酰硫基-十一碳烯基）; 和16; 5-氨基-1,10-菲咯啉-（16-乙酰硫基十六烷基）。可溶于有机介质的烷基乙酰硫基化配合物在水溶液中形成低多分散性的纳米聚集体。根据动态光散射，对于[Ru（dpp）₂（N∧N）]（PF ₆）₂ 5×10 ^-6 M水溶液，纳米聚集体直径测量为189 nm和135 nm。分别带有十六烷酰基和己酰基尾巴。纳米聚集体表现出双指数发射衰减，其动力学与并入DPPC脂质体膜中的[Ru（dpp）₂（16-ATAP）] ^2+的动力学紧密匹配。细胞通透性和[Ru（dpp）₂（11-ATAP）] ²⁺或[Ru（dpp）₂（16-ATAP）] ^2+的分布在活的HeLa和CHO细胞系中进行了详细评估，并从水介质中发现纳米聚集体复合物自发穿过哺乳动物细胞的膜。这个过程似乎是在依赖于温度的研究被激活的基础上进行的。活细胞的荧光成像显示，复合物高度特异性地定位在细胞器内，并且细胞器定位在将侧链烷基链从C16切换到C11以及细胞系同一性方面发生了巨大变化。我们的数据表明，与使用生物分子载体相比，以这种方式能够自组装成纳米囊泡的金属配合物可能是促进细胞膜通透性和驱动选择性靶向的有用手段，该方法既简便又成本相对较低。