Nano-Scaled Zeolitic Imidazole Framework-8 as an Efficient Carrier for the Intracellular Delivery of RNase A in Cancer Treatment

摘要

Background: Zeolitic imidazole framework-8 (ZIF-8) as an emerging platform has exhibited great potential in the protein delivery owing to its tunable chemical functionality. Materials and methods: ZIF-8 was employed as a carrier for the encapsulation and intracellular delivery of RNase A, aimed to achieve a rapid release of proteins in an acidic environment. The intracellular uptake of RNase A was studied by confocal laser scanning microscopy (CLSM), and the inhibition of cell proliferation after the delivery of RNase A was evaluated by MTT assay, Live/Dead staining, and TUNEL cell apoptosis analysis, using human lung adenocarcinoma cell line A549 as a model. The biocompatibility of RNase A@ZIF-8 nanoparticles was systematically detected through the hemolysis and cytotoxicity assay. Results: The RNase A@ZIF-8 nanoparticles constructed by biomimetic mineralization could not only facilitate the encapsulation of protein molecules (protein loading: 13.4%) but also maintain the enzymatic activity and stability of RNase A. The CLSM images showed that RNase A@ZIF-8 nanoparticles could efficiently improve the intracellular uptake of RNase A. Moreover, RNase A@ZIF-8 nanoparticles could obviously inhibit the cell proliferation through the induction of cell apoptosis, with 31.3% of cell death at an RNase A concentration of 10 μg/mL. Finally, RNase A@ZIF-8 nanoparticles were elucidated to possess excellent biocompatibility, with hemolysis of 5% using the same concentration of RNase A@ZIF-8. Conclusion: ZIF-8 could be used as an effective carrier to deliver the therapeutic protein RNase A into the cytosol, which will be beneficial for improving the efficacy of cancer treatment.