单克隆抗体功能化的脂质体为癌症提供靶向治疗，具有药物持续释放、稳定性增强、在肿瘤中被动积累以及与癌细胞上过度表达的受体相互作用等优点。本研究旨在开发和表征载有卡巴他赛的抗 EGFR 免疫脂质体，并评估其体外和体内抗前列腺癌的特性。采用 Box-Behnken 设计，含有大豆磷脂酰胆碱、10% 胆固醇和 1:20 药物脂质比的配方产生纳米级粒径、低多分散性和高药物封装性。免疫脂质体通过 DSPE-PEG-马来酰亚胺脂质锚与西妥昔单抗缀合。表征证实了完整的抗体结构以及缀合后与 EGFR 受体的相互作用。固态分析证实，卡巴他赛以无定形状态分散在脂质体内。体外释放研究表明卡巴他赛从免疫脂质体中释放较慢。免疫脂质体在 EGFR 过表达 DU145 细胞中增强了卡巴他赛的细胞毒性，而不影响非肿瘤 L929 细胞。西妥昔单抗在 EGFR 过度表达的前列腺癌细胞中以时间依赖性方式改善细胞摄取发挥了重要作用。在体内，免疫脂质体导致异种移植小鼠的肿瘤显着消退，提高存活率并减少体重减轻。虽然卡巴他赛引起白细胞减少，与临床结果一致，但组织学分析显示没有明显的毒性。总之，免疫脂质体显示出适合卡巴他赛递送的物理化学特性，对表达 EGFR 的前列腺癌细胞具有高细胞摄取的细胞毒性，并在体内诱导显着的肿瘤消退，且全身毒性可控。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Liposomes functionalized with monoclonal antibodies offer targeted therapy for cancer, boasting advantages like sustained drug release, enhanced stability, passive accumulation in tumors, and interaction with overexpressed receptors on cancer cells. This study aimed to develop and characterize anti-EGFR immunoliposomes loaded with cabazitaxel and assess their properties against prostate cancer in vitro and in vivo. Using a Box-Behnken design, a formulation with soy phosphatidylcholine, 10% cholesterol, and a 1:20 drug-lipid ratio yielded nanometric particle size, low polydispersity and high drug encapsulation. Immunoliposomes were conjugated with cetuximab through DSPE-PEG-Maleimide lipid anchor. Characterization confirmed intact antibody structure and interaction with EGFR receptor following conjugation. Cabazitaxel was dispersed within the liposomes in the amorphous state, confirmed by solid-state analyses. In vitro release studies showed slower cabazitaxel release from immunoliposomes. Immunoliposomes had enhanced cabazitaxel cytotoxicity in EGFR-overexpressing DU145 cells without affecting non-tumor L929 cells. Cetuximab played an important role to improve cellular uptake in a time-dependent fashion in EGFR-overexpressing prostate cancer cells. In vivo, immunoliposomes led to significant tumor regression, improved survival, and reduced weight loss in xenograft mice. While cabazitaxel induced leukopenia, consistent with clinical findings, histological analysis revealed no evident toxicity. In conclusion, the immunoliposomes displayed suitable physicochemical properties for cabazitaxel delivery, exhibited cytotoxicity against EGFR-expressing prostate cancer cells, with high cell uptake, and induced significant tumor regression in vivo, with manageable systemic toxicity.Copyright © 2024 Elsevier B.V. All rights reserved.