P53 Gene Therapy with ZIF-8 Metal-Organic Framework: A Platform in Cancer Gene Therapy

Gene therapy holds great promise as a therapeutic approach for combating cancer, with the choice of gene delivery vector being a critical factor in its success. In recent years, metal-organic frameworks (MOFs) have emerged as valuable tools for intracellular plasmid delivery in this field. This study aimed to encapsulate plasmid DNA encoding the TP53 tumor suppressor gene (pEGFP-N1-TP53) within zeolitic imidazolate framework-8 (ZIF-8) MOFs and ZIF-8-PEI. Subsequently, the transfection efficiency and ability to induce cell death were assessed in MDA-MB-231, MCF-7, and HeLa cancer cells. A comparative analysis was conducted to evaluate the induction of cell death by pEGFP-N1-TP53@ZIF-8-PEI, pEGFP-N1-TP53-ZIF-8 nanoparticles, and Lipofectamine in the aforementioned cell lines. Additionally, an optimal condition for loading the plasmid into ZIF-8 was proposed. The findings from cell transfection assays, MTT assay, and flow cytometry revealed that both pEGFP-N1-TP53@ZIF-8-PEI and pEGFP-N1-TP53-ZIF-8 effectively delivered the plasmid to the cells. Notably, pEGFP-N1-TP53@ZIF-8-PEI exhibited significant results, inducing 77% cell death in the HeLa cell line and 73% in the MDA-MB-231 cell line. Our observations indicated that MDA-MB-231 and HeLa cells exhibited heightened responsiveness to TP53 gene therapy when delivered through ZIF-8-PEI and ZIF-8. Based on these findings, further investigation of pEGFP-N1-TP53@ZIF-8-PEI as a potential cancer therapeutic platform in other cancer cell types is warranted.