Self-assembled pH-responsive polymeric nanoparticles based on lignin-histidine conjugate with small particle size for efficient delivery of anti-tumor drugs

As a natural biomaterial, lignin is mainly obtained from waste in the pulping and papermaking industry, and is becoming an alternative to petroleum-based chemicals. Lignin-based nanoparticles provide new possibilities for value-added utilization. In this work, a novel pH-responsive drug-loaded polymeric nanoparticle platform based on aminated lignin-histidine conjugate and 10-hydroxycamptothecin, AL-His/HCPT NP, is prepared by self-assembly. Based on the acidic microenvironment of tumor cells (endosomes: pH ∼5–6; lysosomes: pH ∼4–5), the AL-His/HCPT NPs are successfully imparted the pH-responsiveness by histidine, a pH-responsive small molecule to achieve triggered drug release. After 19 h of simulated release in vitro, the drug release amount of the nanoparticles was 39.1 % at pH 7.2, 63.1 % at pH 5.5, and 72.5 % at pH 4.5, indicating the pH-responsiveness. Meanwhile, the NPs have relatively small particle size (∼40 nm), which is key to anti-tumor nano-carriers. It is characterized by great biocompatibility, good drug loading performance (∼15.57 wt%), and effective cellular uptake (∼2 times that of pure HCPT). In 4T1 tumor-bearing mice model, the group treated with NPs shows excellent anti-tumor effect (tumor growth inhibition rate: ∼2 times that of pure HCPT) and reduced side effects. These results indicate that AL-His/HCPT NPs have great application prospects in drug delivery.