Molecular Mechanisms of redox-active cerium oxide nanoparticles in inhibition of tumor progression

我们的数据表明，氧化铈纳米颗粒（CNP）的抗癌作用可以通过与经典化疗药物如阿霉素的组合来增强，同时对非致瘤细胞没有损伤作用。此外，与CNP联合使用时，可以降低化疗药物的剂量，以减少对健康（非致瘤性）细胞的有害影响，但不会改变对肿瘤细胞的抗癌作用。这导致了计划项目的以下主要目标：研究氧化铈纳米颗粒抑制肿瘤进展的分子机制，并验证其与多柔比星的联合应用。在计划项目中，将研究CNP单独或与多柔比星联合对肿瘤和健康（非致瘤性）细胞的分子效应，以评估CNP作为抗癌治疗中的分子工具的潜在用途和/或风险，并提高潜在联合治疗的疗效。一方面，我们希望详细了解用CNP和/或阿霉素处理不同细胞类型细胞后的线粒体动力学/质量控制以及线粒体自噬/自噬。另一方面，将在肿瘤和非致瘤细胞上研究CNP和多柔比星单独或联合对半胱氨酸蛋白质组的巯基修饰及其功能后果的影响，以确定未来治疗方法的氧化还原靶点。

Our data show that the anticancer effect of cerium oxide nanoparticles (CNP) can be enhanced by a combination with classical chemotherapeutics such as doxorubicin, in parallel having no damaging effect on non-tumorigenic cells. In addition, the dose of the chemotherapeutical drug can be lowered in a combination with CNP to decrease the harmful effect on healthy (non-tumorigenic)) cells, but without changing the anticancer effect on tumor cells. That leads to the following main objectives of the planned project:Studies on the molecular mechanims of cerium oxide nanoparticles to inhibit tumor progression and validation of their application in a combinational approach with doxorubicin.In the planned project, the molecular effects of CNP alone or in combination with doxorubicin will be studied on tumor and healthy (non-tumorigenic) cells to evaluate the potential use and/or risk of CNP as a molecular tool in an anticancer therapy and to increase the efficacy of a potential combination therapy. On the one hand, we want to have a detailed look on the mitochondrial dynamics/quality control as well as mitophagy/autophagy after treatment the different cell types cells with CNP and/or doxorubicin. On the other hand, the effect of CNP and doxorubicin alone or in combination on the thiol modification of the cysteine proteome and its functional consequence will be studied on tumor and non-tumorigenic cells to determine redox targets for future therapeutical approaches.