Improving the Cellular Internalization of Zr(IV) Nanocages by Tuning Hydrophilicity and Lipophilicity

Nanoscale molecular materials have emerged as a new class of compounds at the nanometer scale with well-defined chemical structures, remarkable uniformity and high reproducibility. Among these materials, zirconium-based metal-organic cages (MOCs) have attracted significant attention due to their exceptional stability and applications in catalysis, recognition and separation and so on. However, their poor water solubility impedes their biomedical applications. In this study, decorating the ligand with Ru(II) complexes can not only improve the water solubility but also endow bright red fluorescence with large Stokes shift (180 nm). Notably, butyl-modification of the cyclopentadiene rings can significantly enhance the cell uptake (100 folds) of nanocages via actin- and dynamin-mediated endocytosis. The unique advantages and easy modifiability of these nanocages make them highly promising candidates for diverse biological applications.