Engineered Dual pH/GSH-Responsive Lignin-Based Nanocarriers for Enhanced Tumor Growth Inhibition

In this study, we designed a lignin-based nanocarrier system with dual-stimuli responsiveness to the acidic pH and elevated glutathione (GSH) levels in the tumor microenvironment, and doxorubicin (DOX) was loaded to develop a nanomedicine delivery platform for antitumor treatment. Under the optimized conditions, uniform lignin-based nanoparticles with a diameter of approximately 150 nm and well-controlled physicochemical properties were successfully prepared. In vitro release studies confirmed the selective drug release under simulated tumor conditions (pH 6.5, 10 mM GSH). Biological evaluation revealed that the drug-loaded nanoparticles exhibited potent cytotoxicity against 4T1 breast cancer cells, while maintaining over 85% viability in normal cells, indicating good biocompatibility. In 4T1 tumor-bearing mice, the engineered nanocarriers demonstrated significantly enhanced therapeutic efficacy, achieving 71.84% tumor growth inhibition compared to that of 58.78% with free DOX, along with reduced systemic toxicity. In summary, this study demonstrates the successful transformation of sustainable lignin into an efficient therapeutic platform via precise chemical modification, effectively combining biopolymer advantages with stimulus-triggered drug release for more promising and biodegradable nanocarriers for cancer therapy.