1 Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2 Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, China.
J Biomater Appl. 2019 May;33(10):1373-1381. doi: 10.1177/0885328219836540. Epub 2019 Mar 16.
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 FeO-ZIF-8 magnetic nano-composite was fabricated and used for DOX delivery for HCC therapy. The morphology, structure and property of FeO-ZIF-8 nano-composites were evaluated by scanning electron microscopy, transmission electron microscopy and N adsorption-desorption isotherms studies. The drug release from DOX@FeO-ZIF-8 was measured in pH 7.4 phosphate-buffered saline. The cellular uptake ability of DOX@FeO-ZIF-8 into hepatocarcinoma cell line (MHCC97H) was visualized with a confocal laser scanning microscope. The effects of FeO-ZIF-8, DOX and DOX@FeO-ZIF-8 against MHCC97H cells were evaluated by CCK-8 assay and flow cytometry assay. FeO-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 FeO-ZIF-8 nano-composites loaded 120 μg DOX when DOX@FeO-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 FeO-ZIF-8 was nontoxic to MHCC97H cells, and DOX@FeO-ZIF-8 presented effective inhibiting effect on cell viability of MHCC97H cells. Cellular uptake assay showed that DOX@FeO-ZIF-8 accumulated in both cytoplasm and nuclei. Moreover, because of valid drug accumulation, DOX@FeO-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 FeO-ZIF-8, DOX@FeO-ZIF-8 presented enhanced effects on HCC cells compared to free DOX, indicating its potential for the chemotherapy of HCC.
肝细胞癌 (HCC) 是最常见和最恶性的癌症之一,目前尚无有效的治疗方法。化疗药物阿霉素 (DOX) 被广泛用于 HCC 治疗,但由于其临床毒性,其应用受到限制。在本研究中,制备了 FeO-ZIF-8 磁性纳米复合材料,并用于 DOX 递送以进行 HCC 治疗。通过扫描电子显微镜、透射电子显微镜和 N2 吸附-解吸等温线研究评估了 FeO-ZIF-8 纳米复合材料的形态、结构和性能。在 pH7.4 的磷酸盐缓冲液中测量了 DOX@FeO-ZIF-8 的药物释放。通过共聚焦激光扫描显微镜可视化了 DOX@FeO-ZIF-8 进入肝癌细胞系 (MHCC97H) 的摄取能力。通过 CCK-8 测定和流式细胞术测定评估了 FeO-ZIF-8、DOX 和 DOX@FeO-ZIF-8 对 MHCC97H 细胞的作用。合成了 FeO-ZIF-8 纳米复合材料,并将其用作 DOX 的递送纳米载体。由于 ZIF-8 具有高载药性能,当在 30mg/mL DOX 溶液中合成 DOX@FeO-ZIF-8 时,1mg FeO-ZIF-8 纳米复合材料可负载 120μg DOX。累积 DOX 释放曲线显示出随时间的缓慢和持续释放模式。CCK-8 测定结果表明 FeO-ZIF-8 对 MHCC97H 细胞无毒,而 DOX@FeO-ZIF-8 对 MHCC97H 细胞活力具有有效抑制作用。细胞摄取实验表明 DOX@FeO-ZIF-8 在内质网和细胞核中均有积累。此外,由于有效药物积累,DOX@FeO-ZIF-8 对 MHCC97H 细胞的凋亡诱导作用良好。总之,基于 FeO-ZIF-8 的无毒和高载药能力,与游离 DOX 相比,DOX@FeO-ZIF-8 对 HCC 细胞表现出增强的作用,表明其在 HCC 化疗中的潜力。
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