Molecular Design of Dual Redox-Active Phospholipid Polymers with a Potent Anticancer Activity

IF 4.7 2区 化学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Applied Polymer Materials Pub Date : 2025-04-11 DOI:10.1021/acsapm.5c00350
Yuki Ogawa, Masahiro Kaneko* and Akira Ito*, 
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Abstract

Redox-active compounds that disrupt the intracellular redox balance are promising anticancer agents because of the vulnerability of cancer cells to oxidative stress. The conjugation of different redox-active molecules can effectively achieve high therapeutic efficacy but can also lead to challenges owing to their typically poor water solubility and complicated organic synthesis. In this study, we designed a water-soluble, cell-penetrating, dual redox-active polymer (pMBFcAq) containing ferrocene (Fc) and anthraquinone (Aq) units. pMBFcAq retained the redox activity originating from the Fc and Aq units and induced oxidative stress and cell death more strongly against mouse colon cancer CT26 cells than polymers containing either Aq or Fc units alone. The in vitro anticancer activity of pMBFcAq was enhanced by adjusting its composition. Moreover, pMBFcAq significantly suppressed the in vivo growth of CT26 tumors, indicating potent anticancer activity. This study provides a strategy for the development of redox-active polymers with high therapeutic efficacy.

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具有强抗癌活性的双氧化还原活性磷脂聚合物的分子设计
由于癌细胞易受氧化应激的影响,破坏细胞内氧化还原平衡的氧化还原活性化合物是很有前途的抗癌药物。不同氧化还原活性分子的偶联可以有效地获得较高的治疗效果,但由于其水溶性差和复杂的有机合成,也会带来挑战。在这项研究中,我们设计了一种含有二茂铁(Fc)和蒽醌(Aq)单元的水溶性、细胞穿透性、双氧化还原活性聚合物(pMBFcAq)。pMBFcAq保留了源自Fc和Aq单元的氧化还原活性,并比单独含有Aq或Fc单元的聚合物更强烈地诱导小鼠结肠癌CT26细胞的氧化应激和细胞死亡。pMBFcAq的体外抗癌活性可以通过调整其组成来增强。此外,pMBFcAq显著抑制CT26肿瘤的体内生长,表明其具有强大的抗癌活性。本研究为开发具有高疗效的氧化还原活性聚合物提供了一种策略。
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来源期刊
CiteScore
7.20
自引率
6.00%
发文量
810
期刊介绍: ACS Applied Polymer Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics, and biology relevant to applications of polymers. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates fundamental knowledge in the areas of materials, engineering, physics, bioscience, polymer science and chemistry into important polymer applications. The journal is specifically interested in work that addresses relationships among structure, processing, morphology, chemistry, properties, and function as well as work that provide insights into mechanisms critical to the performance of the polymer for applications.
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