Doxorubicin-loaded Fe ₃ O ₄ -ZIF-8 nano-composites for hepatocellular carcinoma therapy

Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers and has no effective therapeutic approaches. Chemotherapeutic drug doxorubicin (DOX) is widely used for HCC therapy, but its application is limited by the clinical toxicity. In the present study, an Fe ₃ O ₄ -ZIF-8 magnetic nano-composite was fabricated and used for DOX delivery for HCC therapy. The morphology, structure and property of Fe ₃ O ₄ -ZIF-8 nano-composites were evaluated by scanning electron microscopy, transmission electron microscopy and N ₂ adsorption-desorption isotherms studies. The drug release from DOX@Fe ₃ O ₄ -ZIF-8 was measured in pH 7.4 phosphate-buffered saline. The cellular uptake ability of DOX@Fe ₃ O ₄ -ZIF-8 into hepatocarcinoma cell line (MHCC97H) was visualized with a confocal laser scanning microscope. The effects of Fe ₃ O ₄ -ZIF-8, DOX and DOX@Fe ₃ O ₄ -ZIF-8 against MHCC97H cells were evaluated by CCK-8 assay and flow cytometry assay. Fe ₃ O ₄ -ZIF-8 nano-composites were synthesized and used as a nano-carrier for the delivery of DOX. Because of high drug loading property of ZIF-8, 1 mg Fe ₃ O ₄ -ZIF-8 nano-composites loaded 120 μg DOX when DOX@Fe ₃ O ₄ -ZIF-8 was synthesized in 30 mg/mL DOX solution. The cumulative DOX release curve showed a slow and sustained release pattern over time. The results of CCK-8 assay showed that Fe ₃ O ₄ -ZIF-8 was nontoxic to MHCC97H cells, and DOX@Fe ₃ O ₄ -ZIF-8 presented effective inhibiting effect on cell viability of MHCC97H cells. Cellular uptake assay showed that DOX@Fe ₃ O ₄ -ZIF-8 accumulated in both cytoplasm and nuclei. Moreover, because of valid drug accumulation, DOX@Fe ₃ O ₄ -ZIF-8 exhibited a good inducing effect on cell apoptosis of MHCC97H cells. In conclusion, based on the nontoxic and high drug loading capability of Fe ₃ O ₄ -ZIF-8, DOX@Fe ₃ O ₄ -ZIF-8 presented enhanced effects on HCC cells compared to free DOX, indicating its potential for the chemotherapy of HCC.