Cheng Zan, Yu Mei, Wan Yilong, Xiang Huandong, Wei Haoran, Zu Xu, Li Xin, Zhang Ruiting, Li Fangshu, Wang Shanshan, She Yongxin
Institute of Quality Standards & Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100049, China.
Nanomaterials (Basel). 2025 May 29;15(11):826. doi: 10.3390/nano15110826.
Metal-organic frameworks (MOFs) have great potential for drug delivery systems due to their tunnel pore size, structural versatility, and high surface area. Among them, UiO-67 have recently attracted substantial attention as functional nanocarriers for effective delivery of small molecule chemical drugs. However, the influence of the size on cellular uptake of UiO-67 remains ambiguous. Here, we use polyvinyl pyrrolidone (PVP) as the capping agent of UiO-67 to synthesize spherical Zr-based MOFs with various diameters, including 40 nm, 60 nm, and 120 nm. The highest cellular uptake is observed in the case of Zr-based MOFs with a diameter of 40 nm (PU MOFs). Moreover, doxorubicin can be loaded into the inner pores of PU MOF via π-π and electrostatic interactions (DPU MOFs), with a loading capacity of 82 wt%, and gradually released under acidic conditions. In vitro, the resulting DPU MOFs can be internalized by cancer cells more effectively, thereby enhancing the delivery of doxorubicin into cancer cells. Ultimately, this results in enhanced antitumor efficacy toward 4T1, Hs 578T, and MCF-7 cells. Our findings indicate that approximately 40 nm may be the optimum diameter for the special Zr-based MOFs to be internalized by cells more effectively, providing potent potential nanocarriers for drug delivery.
金属有机框架材料（MOFs）因其隧道孔径、结构多样性和高比表面积，在药物递送系统方面具有巨大潜力。其中，UiO - 67作为有效递送小分子化学药物的功能性纳米载体，近来备受关注。然而，UiO - 67的尺寸对细胞摄取的影响仍不明确。在此，我们使用聚乙烯吡咯烷酮（PVP）作为UiO - 67的封端剂，合成了直径各异的球形锆基金属有机框架材料，包括40 nm、60 nm和120 nm。在直径为40 nm的锆基金属有机框架材料（PU MOFs）中观察到最高的细胞摄取率。此外，阿霉素可通过π - π和静电相互作用负载到PU MOF的内孔中（DPU MOFs），负载量为82 wt%，并在酸性条件下逐渐释放。在体外，所得的DPU MOFs能更有效地被癌细胞内化，从而增强阿霉素向癌细胞的递送。最终，这导致对4T1、Hs 578T和MCF - 7细胞的抗肿瘤疗效增强。我们的研究结果表明，约40 nm可能是特定锆基金属有机框架材料更有效地被细胞内化的最佳直径，为药物递送提供了强大的潜在纳米载体。
