Dextran-doxorubicin prodrug nanoparticles conjugated with CD147 monoclonal antibody for targeted drug delivery in hepatoma therapy.
Dextran-doxorubicin prodrug nanoparticles conjugated with CD147 monoclonal antibody for targeted drug delivery in hepatoma therapy.
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DOI：
10.1016/j.colsurfb.2023.113400
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发表时间：
2023-06
期刊：
影响因子：
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通讯作者：
Hongrui Tian;Liang Yu;Ming-zu Zhang;Jinlin He;Xingwei Sun;P. Ni
中科院分区：
文献类型：
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作者：
Hongrui Tian;Liang Yu;Ming-zu Zhang;Jinlin He;Xingwei Sun;P. Ni
抗体-药物偶联物（Antibody-drug conjugates，ADC）是近年来发展迅速的一类肿瘤细胞靶向药物。从进一步提高ADC靶向性和开发天然大分子作为药物载体的角度来看，尝试新的靶向给药模式仍然具有挑战性和必要性。在这项研究中，我们开发了一种基于生物大分子葡聚糖（DEX）的抗体修饰的前药纳米粒，用于递送抗肿瘤药物阿霉素（DOX）。首先，氧化葡聚糖（ODEX）与DOX通过Schiff碱反应结合形成ODEX-DOX，其可以自组装成带有醛基的纳米颗粒（NPs）。随后，CD 147单克隆抗体的氨基与ODEX-DOX NP表面上的醛基结合，产生具有相对小的粒度和高DOX负载的酸响应性和抗体修饰的CD 147-ODEX-DOX NP。采用FT-IR、UV-Vis、HPLC和1H NMR等手段对高分子前药ODEX-DOX纳米粒和抗体修饰纳米药物CD 147-ODEX-DOX纳米粒的合成进行了验证。使用动态光散射（DLS）来评估ODEX-DOX NP在不同介质和肿瘤微环境中的稳定性和pH响应性。在PB5.0缓冲溶液中103 h后，DOX的体外总释放量约为70%.体内抗肿瘤实验和生物分布实验证实，CD 147-ODEX-DOX纳米粒能显著抑制HepG 2肿瘤的生长。结果表明，该酸敏纳米药物具有较高的安全性和靶向性。它有望成为未来靶向给药系统和抗癌治疗的理想策略。
Antibody-drug conjugates (ADCs) are a class of tumor cell-targeting drugs that have developed rapidly in recent years. From the perspective of further improving ADC targeting and developing natural macromolecules as drug carriers, it is still challenging and necessary to try new targeted drug delivery modalities. In this study, we have developed an antibody-modified prodrug nanoparticle based on biomacromolecule dextran (DEX) to delivery antitumour drug doxorubicin (DOX). Firstly, oxidized dextran (ODEX) and DOX were bonded to yield ODEX-DOX via Schiff base reaction, which can self-assemble into nanoparticles (NPs) carrying some aldehyde groups. Subsequently, the amino groups of CD147 monoclonal antibody were bound to the aldehyde groups on the surface of ODEX-DOX NPs, resulting in acid-responsive and antibody-modified CD147-ODEX-DOX NPs with relatively small particle size and high DOX loading. FT-IR, UV-Vis, HPLC, and1H NMR were used to demonstrate the successful synthesis of polymer prodrug ODEX-DOX NPs and antibody-modified nanomedicine CD147-ODEX-DOX NPs. Dynamic light scattering (DLS) was used to evaluate the stability and the pH responsiveness of ODEX-DOX NPs in different media and tumour microenvironment. Thein vitrototal release content of DOX reached approximately 70% in PB 5.0 buffer solution after 103 h. Furthermore, thein vivoantitumour efficacy and biodistribution experiments confirmed that CD147-ODEX-DOX NPs could significantly inhibit the growth of HepG2 tumour. All of the results indicate that this acid-sensitive nanomedicine has higher safety and targeting effects. It promises to be an ideal strategy for future targeted drug delivery systems and anticancer therapies.