Abstract 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.

中文翻译：

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基于木质素-组氨酸偶联物的自组装 pH 响应聚合物纳米颗粒，具有小粒径，可有效递送抗肿瘤药物

摘要 作为一种天然生物材料，木质素主要从制浆造纸工业的废弃物中提取，正在成为石油基化学品的替代品。基于木质素的纳米粒子为增值利用提供了新的可能性。在这项工作中，通过自组装制备了一种基于胺化木质素-组氨酸偶联物和 10-羟基喜树碱、AL-His/HCPT NP 的新型 pH 响应型载药聚合物纳米颗粒平台。基于肿瘤细胞的酸性微环境（内体：pH ～5-6；溶酶体：pH ～4-5），AL-His/HCPT NPs 通过组氨酸成功地赋予了 pH 响应性，组氨酸是一种对实现触发式药物释放。体外模拟释放19 h后，纳米粒的药物释放量为pH 7.2时39.1 %，pH 5.5时63.1 %，pH 4.5时72.5 %，指示 pH 响应性。同时，纳米颗粒的粒径相对较小（~40 nm），这是抗肿瘤纳米载体的关键。它的特点是良好的生物相容性、良好的载药性能（~15.57 wt%）和有效的细胞摄取（~纯 HCPT 的 2 倍）。在 4T1 荷瘤小鼠模型中，NPs 治疗组显示出优异的抗肿瘤作用（肿瘤生长抑制率：约 2 倍于纯 HCPT）并减少了副作用。这些结果表明 AL-His/HCPT NPs 在药物递送方面具有广阔的应用前景。在 4T1 荷瘤小鼠模型中，NPs 治疗组显示出优异的抗肿瘤作用（肿瘤生长抑制率：约 2 倍于纯 HCPT）并减少了副作用。这些结果表明 AL-His/HCPT NPs 在药物递送方面具有广阔的应用前景。在 4T1 荷瘤小鼠模型中，NPs 治疗组显示出优异的抗肿瘤作用（肿瘤生长抑制率：约 2 倍于纯 HCPT）并减少了副作用。这些结果表明 AL-His/HCPT NPs 在药物递送方面具有广阔的应用前景。