增强脂肪羟基和羧基的功能性木质素通过促进线粒体功能障碍来减轻骨肉瘤的进展。

IF 5.5 2区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yilin Wang, Yufeng Yuan, Wei Liao, Zaikai Zhuang, Xueying An, Bo Jiang, Chaofeng Zhang, Sehrish Manan, Peng Wang, Yongcan Jin
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引用次数: 0

摘要

木质素是一种复杂的生物聚合物,由于其独特的结构和化学修饰性,在生物医学上有着广阔的应用前景。本研究表明,羟基和羧基修饰的木质素增强了谷胱甘肽的吸附,从而提高了对骨肉瘤的细胞毒性和选择性。修饰木质素通过mPTP激活诱导线粒体功能障碍,导致细胞膜去极化、细胞色素c释放和ATP耗竭,最终触发促凋亡蛋白BAX和抗凋亡蛋白BCL2的下调。此外,木质素处理显著增加活性氧(ROS)水平,同时消耗细胞内GSH,进一步促进氧化应激诱导的细胞凋亡。体内研究证实木质素样品有效抑制肿瘤生长,具有良好的生物安全性。其中,CML的抗癌作用最强。这些发现强调了改性木质素作为一种安全有效的肿瘤治疗药物的潜力,提供了一种新的策略来增强氧化应激介导的肿瘤细胞凋亡,同时保留正常细胞。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Functional Lignin with Enhanced Aliphatic Hydroxyl and Carboxyl Groups to Attenuate Osteosarcoma Progression via Promoting Mitochondrial Dysfunction.

Lignin, a complex biopolymer, has promising biomedical applications due to its unique structure and chemical modifiability. This study shows that lignin modified with hydroxyl and carboxyl groups enhances GSH adsorption, thereby improving cytotoxicity and selectivity against osteosarcoma. The modified lignin induces mitochondrial dysfunction via mPTP activation, resulting in membrane depolarization, cytochrome c release, and ATP depletion, ultimately triggering the pro-apoptotic protein BAX and downregulation of the antiapoptotic protein BCL2. Moreover, lignin treatment significantly increased reactive oxygen species (ROS) levels while depleting intracellular GSH, further promoting oxidative stress-induced apoptosis. In vivo studies confirmed that lignin samples were effective in inhibiting tumor growth with a favorable biosafety profile. Among them, CML showed the strongest anticancer effect. These findings highlight the potential of modified lignin as a safe and effective therapeutic agent for OS treatment, offering a novel strategy to enhance oxidative-stress-mediated tumor cell apoptosis while sparing normal cells.

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来源期刊
Biomacromolecules
Biomacromolecules 化学-高分子科学
CiteScore
10.60
自引率
4.80%
发文量
417
审稿时长
1.6 months
期刊介绍: Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.
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