Chen ZhiFeng, Liu WenLing, Zeng ZiJian, Yan ZhiHong, Ma LiHeng, Liu Yi, Cao XianShuo
Department of Radiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People's Republic of China.
School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, 528458, People's Republic of China.
Int J Nanomedicine. 2025 Aug 20;20:10089-10100. doi: 10.2147/IJN.S528334. eCollection 2025.
This study designed a dopamine derivative integrating active targeting and pH-responsive borate ester bond-mediated passive targeting to construct drug delivery systems for tumor-targeted drug delivery, thus improving antitumor drug bioavailability and expanding the application of dopamine in drug delivery.
Nuclear magnetic resonance and Fourier transform infrared spectrometry were used to determine the structures of Man-PBA-DAO and Man-2PBA-DAO. Hydrodynamic diameter measurements confirmed the pH responsiveness of the targeting nanoparticles in different pH media over 12 hours. Nanoparticle toxicity was assessed using the MTT assay. Cellular uptake of the targeting nanoparticles was evaluated using flow cytometry and fluorescence microscopy. High-performance liquid chromatography (HPLC) was employed to quantify curcumin content.
Covalent binding of mannose molecules to the dopamine derivative molecule allowed it to specifically target A549 cells with mannose receptors. More importantly, a significantly accelerated drug release (about 62% at pH=5.0) at low pH values was achieved by regulating the number of acidic-responsive borate bonds in polymer main chains. As a result, due to active targeting of mannose and passive targeting of acid response, Curcumin-loaded nanoparticles offer remarkably enhanced inhibiting efficiency against A549 cells at a low concentration of 6.25 μg/mL.
The dopamine derivative Man-2PBA-DAO-constructed dual active-passive targeting nano micelles enabled precise delivery and controllable release of Cur, offering new prospects for dopamine-based drug delivery in lung cancer treatment.
本研究设计了一种整合主动靶向和pH响应硼酸酯键介导的被动靶向的多巴胺衍生物，以构建用于肿瘤靶向给药的药物递送系统，从而提高抗肿瘤药物的生物利用度，并拓展多巴胺在药物递送中的应用。
采用核磁共振和傅里叶变换红外光谱法测定甘露糖 - 对苯硼酸 - 多巴胺（Man - PBA - DAO）和甘露糖 - 二对苯硼酸 - 多巴胺（Man - 2PBA - DAO）的结构。通过测定流体动力学直径证实了靶向纳米粒子在不同pH介质中12小时内的pH响应性。使用MTT法评估纳米粒子的毒性。采用流式细胞术和荧光显微镜评估靶向纳米粒子的细胞摄取。采用高效液相色谱法（HPLC）定量姜黄素含量。
甘露糖分子与多巴胺衍生物分子的共价结合使其能够通过甘露糖受体特异性靶向A549细胞。更重要的是，通过调节聚合物主链中酸响应性硼酸酯键的数量，在低pH值下实现了显著加速的药物释放（pH = 5.0时约为62%）。因此，由于甘露糖的主动靶向和酸响应的被动靶向，载姜黄素的纳米粒子在6.25μg/mL的低浓度下对A549细胞具有显著增强的抑制效率。
由多巴胺衍生物Man - 2PBA - DAO构建的主动 - 被动双重靶向纳米胶束能够实现姜黄素的精确递送和可控释放，为基于多巴胺的药物递送在肺癌治疗中提供了新的前景。
