Multidrug resistance is the main obstacle to cancer chemotherapy. Overexpression of drug efflux pumps causes excessive drug efflux from cancer cells, ultimately leading to drug resistance. Hereby, we raise an effective strategy to overcome multidrug resistance using a synergistic combination of membranolytic antitumor β-peptide polymer and chemotherapy drugs. This membrane-active β-peptide polymer promotes the transmembrane transport of chemotherapeutic drugs by increasing membrane permeability and enhances the activity of chemotherapy drugs against multidrug-resistant cancer cells. As a proof-of-concept demonstration, the synergistic combination of β-peptide polymer and doxorubicin (DOX) is substantially more effective than DOX alone against drug-resistant cancer both in vitro and in vivo. Notably, the synergistic combination maintains a potent anticancer activity after continuous use. Collectively, this combination therapy using membrane lytic β-peptide polymer appears to be an effective strategy to reverse anticancer drug resistance.

中文翻译：

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通过化疗药物与溶膜抗肿瘤β-肽聚合物的协同组合逆转抗癌耐药性

多重耐药性是癌症化疗的主要障碍。药物外排泵的过度表达会导致癌细胞过量的药物外流，最终导致耐药性。因此，我们提出了一种有效的策略，利用膜溶解抗肿瘤β-肽聚合物和化疗药物的协同组合来克服多药耐药性。这种膜活性β肽聚合物通过增加膜通透性促进化疗药物的跨膜转运，增强化疗药物针对多重耐药癌细胞的活性。作为概念验证的证明，β-肽聚合物和阿霉素 (DOX) 的协同组合在体外和体内对抗耐药癌症方面比单独使用 DOX 更有效。值得注意的是，这种协同组合在连续使用后仍能保持有效的抗癌活性。总的来说，这种使用膜溶解性β-肽聚合物的联合疗法似乎是逆转抗癌药物耐药性的有效策略。