Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Key Laboratory of Cleaner Production and Integrated Resource Utilization of China National Light Industry, Beijing Technology and Business University, Beijing 100048, China.
Molecules. 2022 Aug 26;27(17):5484. doi: 10.3390/molecules27175484.
Dihydromyricetin (DHM) has garnered attention due to its promising antitumor activity, but its low bioavailability restricts its clinical application. Thus, developing nano-drug delivery systems could enhance its antitumor activity. We prepared DHM@ZIF-8 nanoparticles using the zeolite imidazole framework-8 (ZIF-8) as a carrier loaded with dihydromyricetin. A series of characterizations were performed, including morphology, particle size, zeta potential, X-single crystal diffraction, ultraviolet spectroscopy, infrared spectroscopy, and Brunauer-Emmett-Teller (BET). The in vitro release characteristics of DHM@ZIF-8 under pH = 5.0 and pH = 7.4 were studied using membrane dialysis. The antitumor activity and pro-apoptotic mechanism of DHM@ZIF-8 were investigated through CCK-8 assay, reactive oxygen species (ROS), Annexin V/PI double-staining, transmission electron microscopy, and Western blot. The results depicted that DHM@ZIF-8 possessed a regular morphology with a particle size of 211.07 ± 9.65 nm (PDI: 0.19 ± 0.06) and a Zeta potential of -28.77 ± 0.67 mV. The 24 h drug releasing rate in PBS solution at pH = 7.4 was 32.08% and at pH = 5.0 was 85.52% in a simulated tumor micro acid environment. DHM@ZIF-8 could significantly enhance the killing effect on HepG2 cells compared to the prodrug. It can effectively remove ROS from the tumor cells, promote apoptosis, and significantly affect the expression of apoptosis-related proteins within tumor cells.
二氢杨梅素（DHM）具有抗肿瘤活性，受到广泛关注，但由于其生物利用度低，限制了其临床应用。因此，开发纳米药物递送系统可以提高其抗肿瘤活性。我们使用沸石咪唑酯骨架-8（ZIF-8）作为载体，制备了负载二氢杨梅素的 DHM@ZIF-8 纳米粒子。进行了一系列的表征，包括形貌、粒径、Zeta 电位、X-单晶衍射、紫外光谱、红外光谱和 Brunauer-Emmett-Teller（BET）。采用膜透析法研究了 DHM@ZIF-8 在 pH = 5.0 和 pH = 7.4 下的体外释放特性。通过 CCK-8 法、活性氧（ROS）、Annexin V/PI 双染色、透射电子显微镜和 Western blot 研究了 DHM@ZIF-8 的抗肿瘤活性和促凋亡机制。结果表明，DHM@ZIF-8 具有规则的形态，粒径为 211.07 ± 9.65nm（PDI：0.19 ± 0.06），Zeta 电位为-28.77 ± 0.67mV。在 pH = 7.4 的 PBS 溶液中，24 小时药物释放率为 32.08%，在模拟肿瘤微酸环境中 pH = 5.0 时为 85.52%。与前药相比，DHM@ZIF-8 能显著增强对 HepG2 细胞的杀伤作用。它可以有效地从肿瘤细胞中清除 ROS，促进细胞凋亡，并显著影响肿瘤细胞中凋亡相关蛋白的表达。
