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Selenium-driven enhancement of synergistic cancer chemo-/radiotherapy by targeting nanotherapeutics

机译：通过靶向纳米治疗方法，硒驱动协同癌症化学/放射治疗

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摘要

To overcome drug resistance in hypoxic tumors and the limitations of radiation impedance and radiation dose, we developed a nano-radiosensitizer to improve the efficacy of cancer radiotherapy. We used multifunctional mesoporous silica nanoparticles (MSNs) as the carriers for a novel anticancer selenadiazole derivative (SeD) and modified its surface with folic acid (FA) to enhance its cervical cancer-targeting effects, forming the nanosystem named SeD@MSNs-FA. Upon radiation, SeD@MSNs-FA inhibits the growth of cervical cancer cells by inducing apoptosis through the death receptor-mediated apoptosis pathway and S phase arrest, significantly improving the sensitivity of cervical cancer cells to X-ray radiation. The combined activity of SeD@MSN-FA and radiation can promote excessive production of intracellular reactive oxygen species (ROS) and induce cell apoptosis by affecting p53, protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) pathways. Furthermore, SeD@MSNs-FA can effectively inhibit tumor growth of xenografted HeLa tumors in nude mice. The toxicity analysis of SeD@MSNs-FA nanoparticles in vivo and the histological analysis performed in the mouse model showed that under the current experimental conditions, the nanoparticles induced no significant damage to the heart, liver, spleen, lungs, kidneys, or other major organs. Taken together, this study provides a translational nanomedicine-based strategy for the simultaneous chemo- and radiotherapy of cervical cancer and sheds light on potential mechanisms that can be used to overcome radiotherapeutic resistance.
机译：为了克服缺氧肿瘤的耐药性和辐射阻抗和辐射剂量的局限性，我们开发了一种纳米辐射敏化剂，以提高癌症放射疗法的疗效。我们使用多功能介孔二氧化硅纳米粒子（MSN）作为新型抗癌硒二唑衍生物（SED）的载体，并用叶酸（FA）改性其表面，以增强其宫颈癌靶向效果，形成名为SED @ MSNS-FA的纳米系统。在辐射时，SED @ MSNS-FA通过死亡受体介导的凋亡途径和S期阻滞诱导凋亡，从而提高宫颈癌细胞对X射线辐射的敏感性来抑制宫颈癌细胞的生长。 SED @ MSN-FA和辐射的组合活性可以通过影响P53，蛋白激酶B（AKT）和丝裂剂活化的蛋白激酶（MAPK）途径来促进细胞内反应性氧物质（ROS）和诱导细胞凋亡的过度产生。此外，SED @ MSNS-FA可以有效地抑制裸鼠中异种移植HELA肿瘤的肿瘤生长。体内SED @ MSNS-FA纳米粒子的毒性分析和小鼠模型中进行的组织学分析表明，在目前的实验条件下，纳米颗粒对心脏，肝脏，脾，肺，肾脏或其他主要没有显着损害器官。在一起，该研究提供了一种基于宫颈癌的同时化学和放射治疗的平移纳米医生的策略，并在可用于克服放射治疗抗性的潜在机制上脱光。

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  • 来源
    《Biomaterials Science》 |2021年第13期|共10页
  • 作者

    Liu Xinxin; Yuan Zhongwen; Tang Zheng; Chen Qi; Huang Jiarun; He Lizhen; Chen Tianfeng;

  • 作者单位

    Jinan Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510632 Peoples R China;

    Jinan Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510632 Peoples R China;

    Jinan Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510632 Peoples R China;

    Jinan Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510632 Peoples R China;

    Jinan Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510632 Peoples R China;

    Jinan Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510632 Peoples R China;

    Jinan Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510632 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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