Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China.
Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China.
Bioorg Med Chem. 2022 Sep 1;69:116885. doi: 10.1016/j.bmc.2022.116885. Epub 2022 Jun 14.
The combination of chemodynamic therapy (CDT) and chemotherapy is a promising strategy to achieve enhanced anticancer effects. Metal-organic frameworks (MOFs), as multifunctional drug delivery vehicles, have received extensive attention in the biomedical field. Carbohydrate has excellent biocompatibility and targeting ability, which can be used as a targeting ligand due to a specific recognition with glycoprotein receptors that overexpress on cancer cell membranes. Herein, the pH-responsive mannose-modified ferrocene MOFs with rare earth metal were synthesized via coordination-driven self-assembly of 1,1'-Ferrocenedicarboxylic acid and ytterbium chloride. Subsequently, DOX@Fc-MOFs-Mann nanoparticles (NPs) were obtained by loading doxorubicin (DOX) and modifying mannose (Mann), where DOX@Fc-MOFs-Mann NPs were able to precisely target HepG2 cells via mannose receptor and slowly decompose in the acidic environment of tumor to release ferrocene, DOX, and Yb. Fe in ferrocene effectively activated Fenton reaction to produce high levels of reactive oxygen species (ROS) for irreversible induction of cell apoptosis or necroptosis. Combined with the chemotherapy (CT) ability of DOX, Yb further induced cell death through its own toxicity to successfully achieved the rare earth metal synergistic CDT and CT combination therapy. This synergistic CDT and CT strategy not only opens up new horizons for rare earth metals in biomedical applications but also provides new inspiration into the construction of glycosyl-modified MOFs.
化学动力学治疗（CDT）与化疗相结合是增强抗癌效果的一种很有前途的策略。金属有机框架（MOFs）作为多功能药物载体，在生物医学领域受到了广泛关注。碳水化合物具有极好的生物相容性和靶向能力，由于其与癌细胞膜上过度表达的糖蛋白受体具有特异性识别，因此可以用作靶向配体。本文通过 1,1'-二茂铁二羧酸和氯化镱的配位驱动自组装，合成了 pH 响应的甘露糖修饰的具有稀土金属的二茂铁 MOFs。随后，通过装载阿霉素（DOX）和修饰甘露糖（Mann），得到了 DOX@Fc-MOFs-Mann 纳米粒子（NPs），其中 DOX@Fc-MOFs-Mann NPs 能够通过甘露糖受体精确靶向 HepG2 细胞，并在肿瘤的酸性环境中缓慢分解，以释放二茂铁、DOX 和 Yb。二茂铁中的 Fe 有效地激活了芬顿反应，产生了高水平的活性氧（ROS），从而不可逆地诱导细胞凋亡或坏死。结合 DOX 的化疗（CT）能力，Yb 还通过自身毒性进一步诱导细胞死亡，成功实现了稀土金属协同 CDT 和 CT 联合治疗。这种协同 CDT 和 CT 策略不仅为稀土金属在生物医学应用中开辟了新的视野，也为糖基修饰的 MOFs 的构建提供了新的启示。
