木质素
化学
活性氧
生物高聚物
生物相容性
癌细胞
细胞凋亡
细胞毒性
生物化学
体外
有机化学
癌症
聚合物
生物
遗传学
作者
Yilin Wang,Zhiqiang Lu,Bin Liu,Farzad Seidi,Chaofeng Zhang,Bo Jiang,Caoxing Huang,Huining Xiao,Peng Wang,Yongcan Jin
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-01-23
卷期号:18 (5): 4329-4342
被引量:1
标识
DOI:10.1021/acsnano.3c09924
摘要
Lignin, as an abundant aromatic biopolymer in plants, has great potential for medical applications due to its active sites, antioxidant activity, low biotoxicity, and good biocompatibility. In this work, a simple and ecofriendly approach for lignin fractionation and modification was developed to improve the antitumor activity of lignin. The lignin fraction KL-3 obtained by the lignin gradient acid precipitation at pH = 9–13 showed good cytotoxicity. Furthermore, the cell-feeding lignin after additional structural modifications such as demethylation (DKL-3), sulfonation (SL-3), and demethylsulfonation (DSKL-3) could exhibit higher glutathione responsiveness in the tumor microenvironment, resulting in reactive oxygen species accumulation and mitochondrial damage and eventually leading to apoptosis in HepG2 cells with minimal damage to normal cells. The IC50 values for KL-3, SL-3, and DSKL-3 were 0.71, 0.57, and 0.41 mg/mL, respectively, which were superior to those of other biomass extractives or unmodified lignin. Importantly, in vivo experiments conducted in nude mouse models demonstrated good biosafety and effective tumor destruction. This work provides a promising example of constructing carrier-free functionalized lignin antitumor materials with different structures for inhibiting the growth of human hepatocellular carcinoma (HepG2) cells, which is expected to improve cancer therapy outcomes.
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