华东理工大学刘润辉研究团队报道了化疗药物与膜溶性抗肿瘤β-肽聚合物协同作用逆转抗癌耐药。相关研究成果于2024年4月11日发表在《美国化学会杂志》。

多药耐药性是癌症化疗的主要障碍。药物外排泵的过度表达导致癌症细胞过度药物外排，最终导致耐药性。

该文中，研究人员提出了一种有效的策略，使用膜溶性抗肿瘤β肽聚合物和化疗药物的协同组合来克服多药耐药性。这种具有膜活性的β肽聚合物通过增加膜通透性来促进化疗药物的跨膜转运，并增强化疗药物对耐多药癌症细胞的活性。

作为概念验证，β-肽聚合物和阿霉素（DOX）的协同组合，在体外和体内对耐药癌症的疗效显著高于单独使用DOX。值得注意的是，协同组合在连续使用后保持有效的抗癌活性。总之，这种使用膜裂解β肽聚合物的联合治疗，似乎是逆转抗癌耐药性的有效策略。

附：英文原文

Title: Reversing Anticancer Drug Resistance by Synergistic Combination of Chemotherapeutics and Membranolytic Antitumor β-Peptide Polymer

Author: Ning Shao, Ling Yuan, Longqiang Liu, Zihao Cong, Jiangzhou Wang, Yueming Wu, Runhui Liu

Issue&Volume: April 11, 2024

Abstract: 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.

DOI: 10.1021/jacs.4c00434

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c00434