Doxorubicin-loaded Fe3O4-ZIF-8 nano-composites for hepatocellular carcinoma therapy

阿霉素 材料科学 扫描电子显微镜 药物输送 核化学 肝细胞癌 透射电子显微镜 流式细胞术 毒品携带者 生物医学工程 化学 纳米技术 复合材料 化疗 癌症研究 医学 生物 外科 分子生物学
作者
Chong Cheng,Cheng Li,Xingmei Zhu,Wei Han,Jianhui Li,Yi Lv
出处
期刊:Journal of Biomaterials Applications [SAGE]
卷期号:33 (10): 1373-1381 被引量:27
标识
DOI:10.1177/0885328219836540
摘要

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.
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