Many drug delivery systems end up in the lysosome because they are built from covalent or kinetically inert supramolecular bonds. To reach other organelles, nanoparticles hence need to either be made from a kinetically labile interaction that allows re-assembly of the nanoparticles inside the cell following endocytic uptake, or, be taken up by a mechanism that short-circuits the classical endocytosis pathway. In this work, the intracellular fate of nanorods that self-assemble via the Pt…Pt interaction of cyclometalated platinum(II) compounds, is studied. These deep-red emissive nanostructures (638 nm excitation, ≈700 nm emission) are stabilized by proteins in cell medium. Once in contact with cancer cells, they cross the cell membrane via dynamin- and clathrin-dependent endocytosis. However, time-dependent confocal colocalization and cellular electron microscopy demonstrate that they directly move to mitochondria without passing by the lysosomes. Altogether, this study suggests that Pt…Pt interaction is strong enough to generate emissive, aggregated nanoparticles inside cells, but labile enough to allow these nanostructures to reach the mitochondria without being trapped in the lysosomes. These findings open new venues to the development of bioimaging nanoplatforms based on the Pt…Pt interaction.

中文翻译：

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基于 Pt…Pt 亲金属相互作用的深红色发光超分子纳米结构的细胞内动态组装

许多药物递送系统最终进入溶酶体，因为它们是由共价或动力学惰性的超分子键构成的。为了到达其他细胞器，纳米颗粒因此需要由动力学不稳定的相互作用制成，允许在细胞内吞后重新组装纳米颗粒，或者通过使经典内吞途径短路的机制来吸收。在这项工作中，研究了通过环金属化铂 (II) 化合物的 Pt…Pt 相互作用自组装的纳米棒的细胞内命运。这些深红色发射纳米结构（638 nm 激发，≈700 nm 发射）由细胞培养基中的蛋白质稳定。一旦与癌细胞接触，它们就会通过依赖于动力蛋白和网格蛋白的内吞作用穿过细胞膜。然而，时间依赖性共聚焦共定位和细胞电子显微镜表明它们直接移动到线粒体而不经过溶酶体。总而言之，这项研究表明 Pt…Pt 相互作用足够强，可以在细胞内产生发射的、聚集的纳米颗粒，但又足够不稳定，可以让这些纳米结构到达线粒体而不被困在溶酶体中。这些发现为基于 Pt…Pt 相互作用的生物成像纳米平台的开发开辟了新的途径。但足够不稳定以允许这些纳米结构到达线粒体而不被困在溶酶体中。这些发现为基于 Pt…Pt 相互作用的生物成像纳米平台的开发开辟了新的途径。但足够不稳定以允许这些纳米结构到达线粒体而不被困在溶酶体中。这些发现为基于 Pt…Pt 相互作用的生物成像纳米平台的开发开辟了新的途径。