在这项研究中，马来酸酐改性木质素（LG-M）、ROS可裂解的缩硫酮（TK）键和聚乙二醇（PEG）被用来合成木质素基共聚物（LG-M（TK）-PEG） 。将阿霉素 (DOX) 连接到 LG-M(TK)-PEG 中的 ROS 可裂解键上，用于制备 ROS 可激活的 DOX 前药 (LG-M(TK-DOX)-PEG)。使用 LG-M(TK-DOX)-PEG 制备尺寸为 125.7 ± 3.1 nm 的纳米颗粒 (NP)，与游离 DOX 相比，它们表现出癌细胞的摄取增强。值得注意的是，纳米颗粒中木质素的存在可以促进乳腺癌 4T1 细胞中 ROS 的产生，而对 L929 正常细胞几乎没有影响。这种选择性作用促进了DOX前药在肿瘤微环境中的特异性激活，从而相对于游离DOX具有优异的肿瘤抑制作用和增强的生物安全性。这项工作证明了 LG-M(TK-DOX)-PEG NP 作为癌症治疗的有效药物递送系统的潜力。

In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.