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

Abstract

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 Fe₃O₄-ZIF-8 magnetic nano-composite was fabricated and used for DOX delivery for HCC therapy. The morphology, structure and property of Fe₃O₄-ZIF-8 nano-composites were evaluated by scanning electron microscopy, transmission electron microscopy and N₂ adsorption-desorption isotherms studies. The drug release from DOX@Fe₃O₄-ZIF-8 was measured in pH 7.4 phosphate-buffered saline. The cellular uptake ability of DOX@Fe₃O₄-ZIF-8 into hepatocarcinoma cell line (MHCC97H) was visualized with a confocal laser scanning microscope. The effects of Fe₃O₄-ZIF-8, DOX and DOX@Fe₃O₄-ZIF-8 against MHCC97H cells were evaluated by CCK-8 assay and flow cytometry assay. Fe₃O₄-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 Fe₃O₄-ZIF-8 nano-composites loaded 120 μg DOX when DOX@Fe₃O₄-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 Fe₃O₄-ZIF-8 was nontoxic to MHCC97H cells, and DOX@Fe₃O₄-ZIF-8 presented effective inhibiting effect on cell viability of MHCC97H cells. Cellular uptake assay showed that DOX@Fe₃O₄-ZIF-8 accumulated in both cytoplasm and nuclei. Moreover, because of valid drug accumulation, DOX@Fe₃O₄-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 Fe₃O₄-ZIF-8, DOX@Fe₃O₄-ZIF-8 presented enhanced effects on HCC cells compared to free DOX, indicating its potential for the chemotherapy of HCC.

Keywords

Nanoparticle doxorubicin drug delivery hepatocellular carcinoma metal organic frameworks

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