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 α,ω-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 supramolecular 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 supramolecular polymeric chemotherapy.

我们基于一种在主链上带有葫芦丝[7]尿嘧啶（CB [7]）的新型水溶性聚合物，开发了一种超分子聚合化学疗法的策略。为此，我们合成了双炔基官能化的CB [7]，并通过点击反应将其与α，ω-二叠氮化物-PEG聚合，以形成所需的基于CB [7]的主链聚合物（聚CB [7]） 。可以将抗癌药奥沙利铂封装在聚-CB的腔内[7]，形成超分子聚合物复合物，对正常细胞的细胞毒性较低。此外，当复合物遇到癌细胞时，奥沙利铂的细胞毒性得以恢复通过用精胺竞争性地替代CB [7]腔中的奥沙利​​铂，可以过量表达精胺，例如结直肠癌细胞。有趣的是，超分子聚合物复合物对癌细胞的细胞毒性高于奥沙利铂本身。细胞毒性的增强应归因于组合作用，这是由于在细胞的微环境中结合了奥沙利铂从超分子聚合复合物中的释放和精胺的减少，因为精胺是细胞生长和增殖所必需的。与奥沙利铂和CB之间的超分子复合物相比，超分子聚合复合物的另一个优势是其在体内的长循环性能[7]。因此，这一研究领域可能为超分子聚合化学疗法开辟新的视野。