One-pot construction of gemcitabine loaded zeolitic imidazole framework for the treatment of lung cancer and its apoptosis induction

Abstract

AbstractThe 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.

Keywords

• Zeolitic imidazole framework
• gemcitabine
• cytotoxicity
• lung cancer
• apoptosis