Construction of Cisplatin-18-Crown-6 Complexes Through Supramolecular Chemistry to Improve Solubility, Stability, and Antitumor Activity

Cisplatin (DDP), a platinum-chelated compound renowned for its antitumor activity, is often utilized in cancer therapy. However, its real-world clinical efficacy is compromised by poor solubility and low stability, which impedes wider clinical application. Our study aimed to address these limitations of DDP through host-guest supramolecular chemistry approaches. We explored the potential of 18-crown-6 as the host molecule to solubilize and stabilize DDP, the guest molecule. Utilizing techniques such as UV-visible spectroscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, and molecular docking, we conducted a comprehensive analysis on the physical state and inclusion mode of the DDP@18-crown-6 complex. Phase solubility studies and Job's plot confirmed that the DDP@18-crown-6 complex significantly enhanced the aqueous solubility of DDP, with an optimal 1:1 binding ratio. Stability analyses revealed that this complex markedly improved the stability of DDP in pure water. Meanwhile, the stabilization effects of DDP@18-crown-6 were remarkably elevated when combined with 0.9% sodium chloride. In vitro antitumor assays in A549 cell lines demonstrated that the DDP@18-crown-6 complex outperformed raw DDP in cytotoxicity, showing a significantly lower IC₅₀ value. This research offered a promising strategy for DDP solubilization and stabilization, facilitating its anticancer therapeutic efficacy.