College of Chemistry, Chemical Engineering and Materials Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Soochow University, Suzhou 215123, PR China.
Intervention Department, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China.
Colloids Surf B Biointerfaces. 2023 Aug;228:113400. doi: 10.1016/j.colsurfb.2023.113400. Epub 2023 Jun 11.
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, and H 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. The in vitro total release content of DOX reached approximately 70% in PB 5.0 buffer solution after 103 h. Furthermore, the in vivo antitumour 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.
抗体药物偶联物（ADCs）是近年来快速发展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，尝试新的靶向药物递送方式仍然具有挑战性和必要性。在本研究中，我们基于生物大分子葡聚糖（DEX）开发了一种抗体修饰的前药纳米颗粒，用于递送抗肿瘤药物阿霉素（DOX）。首先，通过席夫碱反应将氧化葡聚糖（ODEX）和 DOX 键合，得到带有一些醛基的 ODEX-DOX，可自组装成带有醛基的纳米颗粒（NPs）。随后，CD147 单克隆抗体的氨基与 ODEX-DOX NPs 表面的醛基结合，得到具有相对较小粒径和高 DOX 载量的酸响应性和抗体修饰的 CD147-ODEX-DOX NPs。FT-IR、UV-Vis、HPLC 和 H NMR 用于证明聚合物前药 ODEX-DOX NPs 和抗体修饰纳米药物 CD147-ODEX-DOX NPs 的成功合成。动态光散射（DLS）用于评估 ODEX-DOX NPs 在不同介质和肿瘤微环境中的稳定性和 pH 响应性。在 PB 5.0 缓冲溶液中，DOX 的总释放含量在 103 h 后达到约 70%。此外，体内抗肿瘤功效和生物分布实验证实 CD147-ODEX-DOX NPs 可显著抑制 HepG2 肿瘤的生长。所有结果表明，这种酸敏纳米药物具有更高的安全性和靶向性。它有望成为未来靶向药物递送系统和抗癌治疗的理想策略。
