Antitumor Effects of Carrier-Free Functionalized Lignin Materials on Human Hepatocellular Carcinoma (HepG2) Cells

Abstract

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 IC 50 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.

Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release

“…In our previous work, we have found that lignin and its derivative nanoparticles can stimulate ROS generation in 4T1 cells . This could be caused by the glutathione reactivity of lignin in the tumor microenvironment, resulting in the accumulation of ROS and mitochondrial damage . To our knowledge, the combination of lignin-stimulated oxidative stress amplification and ROS-sensitive polymer prodrugs has not been reported.…”

“…Moreover, lignin-based nanomaterials have exhibited cytotoxic effects on various cancer cells, including breast cancer cells , and liver cancer cells, potentially enhancing their therapeutic efficacy. For instance, studies by Wang et al have demonstrated the cytotoxic effects of lignin nanoparticles on liver cancer cells, highlighting their potential as effective agents in cancer therapy .…”

“…Moreover, lignin-based nanomaterials have exhibited cytotoxic effects on various cancer cells, including breast cancer cells , and liver cancer cells, potentially enhancing their therapeutic efficacy. For instance, studies by Wang et al have demonstrated the cytotoxic effects of lignin nanoparticles on liver cancer cells, highlighting their potential as effective agents in cancer therapy . Additionally, lignin-based nanoparticles exhibit efficient loading of lipid-soluble drugs and excellent blood compatibility, positioning them as promising candidates for drug delivery applications.…”