Abstract

The zeolitic imidazole framework (ZIF) is a novel metal-organic framework with distinctive properties, including crystalline form, controllable pore size, wide surface area and biocompatibility. ZIF-L is a good candidate for biological applications due to its outstanding thermal and chemical stabilities. The current study aimed to develop gemcitabine (GEM) encapsulated ZIF-L in a single pot and assess its anticancer efficacy against lung cancer. The GEM@ZIF-L nanoparticles were studied using microscopic and spectroscopic measurements. The outcomes of cell counting kit-8 (CCK-8) demonstrated that two lung cancer cells were significantly cytotoxic to the IC₅₀ values GEM@ZIF-L in A549 and H1299 cells were 9.12 ± 1.28 µg/mL, 5.47 ± 2.90 µg/mL, respectively. A dose-dependent decrease of lung cancer cells (A549 and H1299) was found using GEM@ZIF-L. Additionally, remarkably induced apoptosis was observed in GEM@ZIF-L, validated by fluorescence staining techniques (including acridine orange and ethidium bromide) (AO-EB and nuclear DAPI staining). The mode of cell death was examined by flow cytometry (dual staining Annexin V-FITC/PI) methods. Further, the ELISA analysis confirmed that GEM@ZIF-L induced apoptosis through caspase activation. The multifunctional GEM@ZIF-L nanoparticles may be suitable for biological applications, as the current work demonstrates.

摘要

沸石咪唑骨架（ZIF）是一种新型金属有机骨架，具有独特的性质，包括晶型、可控的孔径、宽的比表面积和生物相容性。ZIF-L 因其出色的热稳定性和化学稳定性而成为生物应用的良好候选者。目前的研究旨在开发单罐封装的吉西他滨 (GEM) ZIF-L，并评估其对肺癌的抗癌功效。使用显微镜和光谱测量研究了 GEM@ZIF-L 纳米颗粒。细胞计数试剂盒-8（CCK-8）的结果表明，两种肺癌细胞对IC _{50具有显着的细胞毒性。}A549 和 H1299 细胞中的 GEM@ZIF-L 值分别为 9.12 ± 1.28 µg/mL、5.47 ± 2.90 µg/mL。使用 GEM@ZIF-L 发现肺癌细胞（A549 和 H1299）呈剂量依赖性减少。此外，在 GEM@ZIF-L 中观察到显着诱导的细胞凋亡，并通过荧光染色技术（包括吖啶橙和溴化乙锭）（AO-EB 和核 DAPI 染色）进行验证。通过流式细胞术（双染色Annexin V-FITC/PI）方法检查细胞死亡模式。此外，ELISA 分析证实 GEM@ZIF-L 通过 caspase 激活诱导细胞凋亡。正如目前的工作所证明的那样，多功能 GEM@ZIF-L 纳米颗粒可能适合生物应用。