Bujalance Fernández Javier, de la Asunción-Nadal Víctor, Jurado Sánchez Beatriz, Escarpa Alberto
Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Universidad de Alcala, Alcala de Henares, Madrid, E-28802, Spain.
Andrés M. Del Río Chemical Research Institute, Alcala de Henares, Madrid, E-28802, Spain.
Small Methods. 2025 Jun 3:e2500724. doi: 10.1002/smtd.202500724.
Herein, the synthesis of macroporous zeolitic imidazole framework (ZIF)-based magnetic micromotors (MMs) for the dual encapsulation of 5-fluorouracil (5-FU) and doxorubicin (DOX), with pH-triggered release is described. The MMs are synthesized in methanolic solutions, using superparamagnetic iron oxide nanoparticles (Fe₃O₄) as seeding agents and magnetic engines. The macroporous structure facilitates the loading of high doses of 5-FU, while DOX is docked on the surface of the MMs. This results in release rates of 72.8 µg mg MMs⁻¹ of 5-FU and 3 µg mg MMs⁻¹ of DOX. The magnetic motion of the MMs enables targeted delivery to predefined locations, allowing interaction with cancer cells in the culture medium. Under acidic conditions, DOX becomes protonated and is released from the surface of the micromotors, demonstrating rapid-release kinetics. Simultaneously, the ZIF-8 structure degrades under these conditions, enabling the sustained release of 5-FU for continuous treatment. This dual-delivery, pH-induced mechanism is demonstrated in vitro using Caco-2 cells as a relevant biological model, revealing a decrease in viability and diffusion of the drugs released into the cells. This is the first magnetic metal-organic framework (MOF)-based MM that is pH-sensitive and capable of sequentially releasing two drugs.
本文描述了用于双重封装5-氟尿嘧啶（5-FU）和阿霉素（DOX）且具有pH触发释放功能的大孔沸石咪唑骨架（ZIF）基磁性微马达（MMs）的合成。这些MMs在甲醇溶液中合成，使用超顺磁性氧化铁纳米颗粒（Fe₃O₄）作为晶种剂和磁性引擎。大孔结构有利于高剂量5-FU的负载，而DOX则对接在MMs的表面。这导致5-FU的释放速率为72.8 μg mg MMs⁻¹，DOX的释放速率为3 μg mg MMs⁻¹。MMs的磁运动能够将其靶向递送至预定位置，使其能够与培养基中的癌细胞相互作用。在酸性条件下，DOX质子化并从微马达表面释放，呈现快速释放动力学。同时，ZIF-8结构在这些条件下会降解，从而使5-FU能够持续释放以进行持续治疗。使用Caco-2细胞作为相关生物学模型在体外证明了这种双重递送、pH诱导的机制，结果显示释放到细胞中的药物使细胞活力降低且扩散。这是首个对pH敏感且能够顺序释放两种药物的基于磁性金属有机骨架（MOF）的MM。
