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

氧化还原活性氧化铈纳米颗粒抑制肿瘤进展的分子机制

• 批准号: 418596969
• 负责人: Professor Dr. Peter Brenneisen, Ph.D.
• 金额: --
• 依托单位: Institut für Biochemie und Molekularbiologie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418596969?language=en
• 关键词: Molecular; Mechanisms; redox; active; cerium

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.

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阿霉素等经典化疗药物组合来增强，同时对非致瘤细胞没有损害作用。此外，与CNP联合使用可以降低化疗药物的剂量，以减少对健康（非致瘤）细胞的有害作用，但不改变对肿瘤细胞的抗癌作用。这导致了该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，并验证其与阿霉素联合应用的应用。在计划项目中，CNP单独或联合使用的分子效应与阿霉素的组合将在肿瘤和健康（非致瘤）细胞上进行研究，以评估 CNP 作为抗癌治疗分子工具的潜在用途和/或风险，并提高潜在联合疗法的功效。一方面，我们希望详细了解用 CNP 和/或多柔比星处理不同细胞类型的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和阿霉素单独或组合对半胱氨酸蛋白质组硫醇修饰的影响及其功能结果，以确定未来治疗方法的氧化还原靶点。