Supramolecular Chemotherapy Based on the Host-Guest Complex of Lobaplatin-Cucurbit[7]uril

This work aimed to develop a supramolecular chemotherapy-based strategy to reduce the cytotoxicity of the antitumor drug lobaplatin (LbPt) toward normal human intestinal cells and recover its antitumor bioactivity toward human intestinal tumor cells. Through hostguest interactions, cucurbit[7]uril (CB[7])-encapsulated LbPt decreased the cytotoxicity of LbPt toward normal human intestinal cells, and even at a concentration of 100.0 mu M, LbPtCB[7] exhibited 77.4% higher safety over a 24 h period compared with LbPt. At pH 6.0, the binding affinity constant (K-a) of CB[7] and spermine was (1.18 +/- 0.12) x 10(6) M-1, which is an order of magnitude higher than that of CB[7] with LbPt [K-a = (2.09 +/- 0.07) x 10(5) M-1]; thus, the encapsulated LbPt can be released from its hostguest complex of LbPtCB[7] through competitive replacement with spermine solution. The LbPtCB[7] complex exhibited good in vitro performance for spermine as a biomarker tumor, as demonstrated with human intestinal tumor cells. These results indicate that LbPt is released from its hostguest complex by spermine in the tumor microenvironment, and supramolecular strategies will likely be extended to other clinical antitumor drugs to decrease their severe side effects in normal tissues and recover their antitumor bioactivity in tumors, which will enrich the field of safe supramolecular chemotherapy.