Assessing the Potential of New Lignin-Based pH-Responsive Nanoparticles as Drug Carriers for Cancer Treatment

Abstract

In this study, we prepared new lignin-based pH-responsive nanoparticles (LG-M(N)-PEG NPs) and their conjugates (LG-M(N-DOX)-PEG NPs) by using polyethylene glycol (PEG), doxorubicin (DOX), and alkaline lignin. In these NPs, the PEG chains were conjugated to lignin by an UV irradiated thiol–ene click reaction. The hydrazine and β-thiopropionate bonds in the NPs could conduct pH-triggered release of both DOX and lignin at an acidic pH in the tumor cells. Results showed that LG-M(N-DOX)-PEG NPs had a moderate particle size (48.3 ± 3.2 nm), significant cytotoxicity against 4T1 cells, and enhanced cellular uptake. Interestingly, the NPs without DOX (LG-M(N)-PEG NPs) could increase intracellular reactive oxygen species generation, induce cell pyroptosis, and result in a selective cytotoxicity to cancer cells. While the LG-M(N-DOX)-PEG NPs could deliver both lignin and DOX, they had favorable carrier-enhanced cytotoxicity and higher cancer cellular uptake compared to free DOX. Moreover, LG-M(N-DOX)-PEG NPs exhibited a clear tumor-inhibiting effect in vivo. Therefore, the NPs described here have great potential application in the drug delivery system.