Evaluation of New Palladium Cages as Potential Delivery Systems for the Anticancer Drug Cisplatin

Self‐assembled metallocages are very promising drug‐delivery systems among supramolecular complexes. Thus, exo‐functionalized Pd2L4 (L=ligand) cages were synthesized and characterized, and the encapsulation of the anticancer drug cisplatin in their cavity has been documented. The antiproliferative effects of the metallocages and their combination with cisplatin were examined in vitro in cancer cell lines, while fluorescence microscopy was used to monitor their uptake. Notably, the hydroxymethyl‐functionalized PdII cage encapsulating cisplatin showed improved cytotoxic effect against human ovarian cancer cells compared to free cisplatin. The toxicity of Pd2L4 cages was evaluated for the first time ex vivo in healthy rat‐liver tissues using the precision cut‐tissue slices technology, demonstrating in some cases scarce effects on liver viability. These results further highlight the potential of self‐assembled Pd2L4 cages for biological applications. Self‐assembled metallocages of the type Pd2L4 are promising delivery vehicles for the anticancer drug cisplatin. Drug encapsulation was proven by different methods, and the biological properties were investigated in cancer cells also with the aid of fluorescence microscopy. The host–guest systems possess improved toxic effects in ovarian cancer cells compared to cisplatin while having limited toxicity in liver tissues (see scheme).