Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, 255049, Shandong, China.
School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, 255049, Shandong, China.
Colloids Surf B Biointerfaces. 2021 Jul;203:111759. doi: 10.1016/j.colsurfb.2021.111759. Epub 2021 Apr 10.
Despite developments in surgery and chemotherapy, effective treatment of breast cancer is still an urgent problem owing to recurrence and metastasis. By combining the advantages of curcumin (Cur), zeolitic imidazolate framework-8 nanoparticles (ZIF-8), and hyaluronic acid (HA) in breast cancer therapy, Cur-loaded and HA-coated ZIF-8 (Cur@ZIF-8@HA) were synthesized using a method based on the pH-dependent solubility of Cur and the electrostatic interactions between zinc ions and carboxyl groups of HA. Cur@ZIF-8 were also prepared as a control group. Comprehensive comparisons of the physicochemical properties and anticancer activities of Cur@ZIF-8@HA and Cur@ZIF-8 were conducted. The results indicated that the degradation of Cur during the synthesis of Cur@ZIF-8 was negligible. The obtained Cur@ZIF-8 and Cur@ZIF-8@HA were truncated cubes with hydrodynamic diameters of 174 and 217 nm, respectively. Cur@ZIF-8@HA possessed better stability during storage in different media, a slower drug release rate under neutral and acidic conditions, and a greater inhibitory effect on breast cancer than Cur@ZIF-8. For 4T1 cells, treatment using Cur@ZIF-8@HA induced more cellular uptake and higher cytotoxicity, accompanied by higher lactate dehydrogenase release, cell cycle arrest in G2/M and S phases, production of reactive oxygen species, and apoptosis. In 4T1 tumor-bearing mice models, Cur@ZIF-8@HA showed a stronger inhibitory effect on tumor growth and pulmonary metastasis. Therefore, Cur@ZIF-8@HA might hold great potential as an agent for the effective therapy of breast cancer.
尽管在手术和化疗方面取得了进展，但由于乳腺癌的复发和转移，有效的治疗方法仍然是一个亟待解决的问题。为了在乳腺癌治疗中结合姜黄素（Cur）、沸石咪唑酯骨架-8 纳米粒子（ZIF-8）和透明质酸（HA）的优势，我们采用了一种基于 Cur 的 pH 依赖性溶解度和锌离子与 HA 羧基之间静电相互作用的方法，合成了载有 Cur 和 HA 包覆的 ZIF-8（Cur@ZIF-8@HA）。还制备了 Cur@ZIF-8 作为对照组。对 Cur@ZIF-8@HA 和 Cur@ZIF-8 的物理化学性质和抗癌活性进行了综合比较。结果表明，在 Cur@ZIF-8 的合成过程中，Cur 的降解可以忽略不计。所得的 Cur@ZIF-8 和 Cur@ZIF-8@HA 均为截角立方体形，水动力学直径分别为 174nm 和 217nm。Cur@ZIF-8@HA 在不同介质中的储存稳定性更好，在中性和酸性条件下的药物释放速度更慢，对乳腺癌的抑制作用大于 Cur@ZIF-8。对于 4T1 细胞，使用 Cur@ZIF-8@HA 进行治疗会引起更多的细胞摄取和更高的细胞毒性，同时伴随着更高的乳酸脱氢酶释放、G2/M 和 S 期的细胞周期停滞、活性氧的产生和细胞凋亡。在 4T1 荷瘤小鼠模型中，Cur@ZIF-8@HA 对肿瘤生长和肺转移具有更强的抑制作用。因此，Cur@ZIF-8@HA 可能具有作为治疗乳腺癌的有效药物的巨大潜力。
