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

Chong Cheng, Cheng Li, Xulong Zhu, Wei Han, Jianhui Li, Yi Lv
Journal of Biomaterials Applications 2019 March 16, : 885328219836540
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 Fe3 O4 -ZIF-8 magnetic nano-composite was fabricated and used for DOX delivery for HCC therapy. The morphology, structure and property of Fe3 O4 -ZIF-8 nano-composites were evaluated by scanning electron microscopy, transmission electron microscopy and N2 adsorption-desorption isotherms studies. The drug release from DOX@Fe3 O4 -ZIF-8 was measured in pH 7.4 phosphate-buffered saline. The cellular uptake ability of DOX@Fe3 O4 -ZIF-8 into hepatocarcinoma cell line (MHCC97H) was visualized with a confocal laser scanning microscope. The effects of Fe3 O4 -ZIF-8, DOX and DOX@Fe3 O4 -ZIF-8 against MHCC97H cells were evaluated by CCK-8 assay and flow cytometry assay. Fe3 O4 -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 Fe3 O4 -ZIF-8 nano-composites loaded 120 μg DOX when DOX@Fe3 O4 -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 Fe3 O4 -ZIF-8 was nontoxic to MHCC97H cells, and DOX@Fe3 O4 -ZIF-8 presented effective inhibiting effect on cell viability of MHCC97H cells. Cellular uptake assay showed that DOX@Fe3 O4 -ZIF-8 accumulated in both cytoplasm and nuclei. Moreover, because of valid drug accumulation, DOX@Fe3 O4 -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 Fe3 O4 -ZIF-8, DOX@Fe3 O4 -ZIF-8 presented enhanced effects on HCC cells compared to free DOX, indicating its potential for the chemotherapy of HCC.

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