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功能化硒纳米系统作为 I 种子的辐射敏化剂用于精确癌症治疗。

Functionalized Selenium Nanosystem as Radiation Sensitizer of I Seeds for Precise Cancer Therapy.

机构信息

Department of Chemistry, Jinan University , Guangzhou 510632, China.

The Third Affiliated Hospital, Sun Yat-sen University , Guangzhou 510630, China.

出版信息

ACS Appl Mater Interfaces. 2017 Aug 9;9(31):25857-25869. doi: 10.1021/acsami.7b07167. Epub 2017 Jul 26.

DOI:10.1021/acsami.7b07167
PMID:28718286
Abstract

Although radiotherapy has been extensively applied in cancer treatment, external beam radiation therapy is still unable to avoid damage to adjacent normal tissues in the process of delivering a sufficient radiation dose to the tumor sites of patients. To overcome this limitation, chemoradiotherapy, as a combination of chemotherapy and radiotherapy of a radioactive seed, has been proposed to decrease the damage to tumor-surrounding tissues and enhance the radiosensitivity of solid tumors. In this study, we designed and synthesized folic acid-conjugated selenium nanoparticles (FA@SeNPs) as a cancer-targeting agent that could be synergistically enhanced by radioactive I seeds to realize anticancer efficacy and inhibited colony formation ability. Interestingly, when compared with X-ray irradiation, I seeds demonstrate a larger synergistic effect with the FA@SeNPs, drastically increasing reactive oxygen species overproduction to trigger apoptosis and influencing the cell cycle distribution in human breast cancer cells, inducing DNA damage and activating the mitogen-activated protein kinase and p53 signaling pathways. Moreover, this combination treatment demonstrates better in vivo antitumor activity and lower systemic toxicity. Therefore, this study demonstrates a new strategy for using functionalized SeNPs as a radiation sensitizer for I seeds for cancer therapy.

摘要

尽管放射疗法已广泛应用于癌症治疗,但在向患者肿瘤部位提供足够辐射剂量的过程中,外部束辐射疗法仍然无法避免对邻近正常组织的损伤。为了克服这一限制,化学放射疗法(化疗与放射性种子放射治疗的结合)已被提出,以减少对肿瘤周围组织的损伤并提高实体瘤的放射敏感性。在这项研究中,我们设计并合成了叶酸偶联硒纳米粒子(FA@SeNPs)作为一种癌症靶向剂,它可以与放射性碘种子协同增强,从而实现抗癌功效并抑制集落形成能力。有趣的是,与 X 射线照射相比,碘种子与 FA@SeNPs 具有更大的协同作用,可大量增加活性氧的产生,从而引发细胞凋亡并影响人乳腺癌细胞的细胞周期分布,诱导 DNA 损伤并激活丝裂原活化蛋白激酶和 p53 信号通路。此外,这种联合治疗在体内显示出更好的抗肿瘤活性和更低的全身毒性。因此,本研究为使用功能化 SeNPs 作为碘种子的辐射增敏剂用于癌症治疗提供了一种新策略。

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