Orthopaedic Research Lab, Aarhus University Hospital, 8000 Aarhus C, Denmark.
Int J Pharm. 2013 May 1;448(1):214-20. doi: 10.1016/j.ijpharm.2013.03.041. Epub 2013 Mar 25.
Little is known about the interaction between antineoplastic drugs and implants in bone cancer patients. We investigated the interaction between commercially available porous tantalum (Ta) implants and the chemotherapeutic drug, Doxorubicin (DOX). DOX solutions were prepared in the presence of Ta implant. The changes in fluorescence intensity of the DOX chromophore were measured by spectrofluorometry and the efficacy of DOX was evaluated by viability of rabbit rectal tumor cells (VX2). After 5 min interaction of the DOX solution (5 μg/ml) with the Ta implant, the fluorescent intensity of the DOX solution was 85% degraded, and only 20% the drug efficacy to kill VX2 cells was retained. However, after adding a reducing agent, Dithiothreitol (DTT, 10 μg/ml), 80% of the original fluorescence and 50% of the drug efficacy were restored while UV irradiation enhanced drug degradation in the presence of Ta implant. The action of DTT and UV irradiation indicated that reactive oxygen species (ROS) were involved in the drug degradation mechanism. We detected that Ta implants in aqueous medium produced hydroxyl radicals. Cells showed higher intracellular ROS activity when culture medium was incubated with the Ta implant prior to cell culture. It is concluded that the porous Ta implant antagonizes the cytotoxicity of DOX via ROS generation of the porous Ta implant.
关于抗肿瘤药物和骨癌患者植入物之间的相互作用知之甚少。我们研究了市售多孔钽（Ta）植入物与化疗药物阿霉素（DOX）之间的相互作用。在 Ta 植入物存在的情况下制备 DOX 溶液。通过荧光分光光度法测量 DOX 发色团荧光强度的变化，并通过兔直肠肿瘤细胞（VX2）活力评估 DOX 的功效。DOX 溶液（5μg/ml）与 Ta 植入物相互作用 5 分钟后，DOX 溶液的荧光强度降解了 85%，而杀死 VX2 细胞的药物功效仅保留了 20%。然而，加入还原剂二硫苏糖醇（DTT，10μg/ml）后，恢复了 80%的原始荧光和 50%的药物功效，而在 Ta 植入物存在的情况下，紫外线照射增强了药物降解。DTT 和紫外线照射的作用表明活性氧（ROS）参与了药物降解机制。我们检测到在水介质中 Ta 植入物产生了羟基自由基。当培养基在细胞培养之前与 Ta 植入物孵育时，细胞显示出更高的细胞内 ROS 活性。结论是多孔 Ta 植入物通过多孔 Ta 植入物产生的 ROS 拮抗 DOX 的细胞毒性。
