Supramolecular polymeric chemotherapy based on cucurbit[7]uril-PEG copolymer

We develop a strategy of supramolecular polymeric chemotherapy based on a new kind of water-soluble polymer that bears cucurbit[7]uril (CB[7]) in the main-chain. To this end, we synthesized a bis-alkynyl functionalized CB[7] and polymerized it with alpha,omega-diazide-PEG through click reaction to form the desired CB[7] based main-chain polymer (poly-CB[7]). Anticancer drug, oxaliplatin, could be encapsulated into the cavity of poly-CB[7] to form a supramolecular polymeric complex, which displayed low cytotoxicity to normal cells. In addition, the cytotoxicity of the oxaliplatin was recovered when the complex met cancer cells that could overexpress spermine, e.g. colorectal cancer cell, through competitive replacement of oxaliplatin from CB[7] cavity by spermine. Interestingly, the cytotoxicity of the supramolecular polymeric complex to cancer cells is higher than oxaliplatin itself. The enhanced cytotoxicity should result from a combined effect by combining the release of oxaliplatin from the supra molecular polymeric complex and decrease of spermine in the micro-environment of the cancer cells, as spermine is needed for cell growth and proliferation. One more advantage of the supramolecular polymeric complex is its long circulation performance in vivo compared with the supramolecular complex between oxaliplatin and CB[7]. Therefore, this line of research may open new horizons for supra molecular polymeric chemotherapy. (C) 2018 Elsevier Ltd. All rights reserved.