Yilin Wang, Yufeng Yuan, Wei Liao, Zaikai Zhuang, Xueying An, Bo Jiang, Chaofeng Zhang, Sehrish Manan, Peng Wang, Yongcan Jin
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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.
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.