Fabrication of pH-responsive temozolomide (TMZ)-clacked tannic acid-altered zeolite imidazole nanoframeworks (ZIF-8) enhance anticancer activity and apoptosis induction in glioma cancer cells

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Abstract
Glioma cancer is the primary cause of cancer-related fatalities globally for both men and women. Traditional chemotherapy treatments for this condition frequently result in reduced efficacy and significant adverse effects. This investigation developed a new drug delivery system for the chemotherapeutic drug temozolomide (TMZ) using pH-sensitive drug delivery zeolitic imidazolate frameworks (ZIF-8). These nanoplatforms demonstrate excellent biocompatibility and hold potential for cancer therapy. Utilizing the favorable reaction milieu offered by ZIFs, a 'one-pot method' was employed for the fabrication and loading of drugs, leading to a good capacity for loading. TMZ@TA@ZIF-8 NPs exhibit a notable response to an acidic milieu, resulting in an enhanced drug release pattern characterized by a controlled release outcome. The effectiveness of TMZ@TA@ZIF-8 NPs in inhibiting the migration and invasion of U251 glioma cancer cells, as well as promoting apoptosis, was confirmed through various tests, including MTT (3-(4,5)-dimethylthiahiazo(-z-y1)) assay, DAPI/PI dual staining, and cell scratch assay. The biochemical fluorescent staining assays showed that TMZ@TA@ZIF-8 NPs potentially improved ROS, reduced MMP, and triggered apoptosis in U251 cells. In U251 cells treated with NPs, the p53, Bax, Cyt-C, caspase-3, -8, and -9 expressions were significantly enhanced, while Bcl-2 expression was diminished. These outcomes show the potential of TMZ@TA@ZIF-8 NPs as a therapeutic agent with anti-glioma properties. Overall, the pH-responsive drug delivery systems we fabricated using TMZ@TA@ZIF-8 NPs show great potential for cancer treatment. This approach has the potential to make significant contributions to the improvement of cancer therapy by overcoming the problems associated with TMZ-based treatments.

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