肝细胞癌（HCC）是一种常见的消化道恶性肿瘤，严重威胁人类的生命和健康。早期的HCC可通过介入治疗、手术和内部放射治疗来治疗，而晚期的选择主要是化疗以延长患者的生存时间。Lenvatinib（LT）是一种已获得美国食品和药物管理局（FDA）批准的前线药物，用于治疗晚期肝癌，并取得了良好的临床疗效。然而，它的溶解性差和严重的副作用不能被忽视。在本研究中，成功构建了一种仿生纳米药物传递平台。该平台由包裹Lenvatinib的pH敏感聚合物，即聚（β-氨基酯）-聚乙二醇-胺（PAE-PEG-NH2）构成的核心和由癌细胞膜（CCM）形成的外壳组成。制备好的纳米药物具有高药物载荷能力、长期稳定性、良好的生物相容性和长时间的保留时间。此外，靶向肿瘤细胞膜和聚合物材料的pH响应特性使它们能够精确靶向肿瘤细胞，在肿瘤微环境中实现响应性释放，从而使它们适用于有效的药物传递。体内实验表明，纳米药物在皮下肿瘤小鼠模型中显示出卓越的肿瘤聚集和治疗效果，并能在21天内有效消除肿瘤。因此，它开辟了一条新的途径，以减少副作用，并提高一线临床用药的特异性治疗效果，用于治疗肿瘤。版权所有©2023 Elsevier B.V. 发布。

Hepatocellular carcinoma (HCC) is a common digestive tract malignancy that seriously threatens human life and health. Early HCC may be treated by intervention, surgery, and internal radiotherapy, while the choice for late HCC is primarily chemotherapy to prolong patient survival. Lenvatinib (LT) is a Food and Drug Administration (FDA)-approved frontline drug for the treatment of advanced liver cancer and has achieved excellent clinical efficacy. However, its poor solubility and severe side effects cannot be ignored. In this study, a bionic nanodrug delivery platform was successfully constructed. The platform consists of a core of Lenvatinib wrapped with a pH-sensitive polymer, namely, poly(β-amino ester)-polyethylene glycol-amine (PAE-PEG-NH2), and a shell formed by a cancer cell membrane (CCM). The prepared nanodrugs have high drug loading capacity, long-term stability, good biocompatibility, and a long retention time. In addition, the targeting effect of tumor cell membranes and the pH-responsive characteristics of the polymer materials enable them to precisely target tumor cells and achieve responsive release in the tumor microenvironment, which makes them suitable for effective drug delivery. In vivo experiments revealed that the nanodrug showed superior tumor accumulation and therapeutic effects in subcutaneous tumor mice model and could effectively eliminate tumors within 21 days. As a result, it opens up a new way to reduce side effects and improve the specific therapeutic effect of first-line clinical medications to treat tumors.Copyright © 2023. Published by Elsevier B.V.