Department of Chemistry, Jinan University , Guangzhou 510632, China.
The Third Affiliated Hospital, Sun Yat-sen University , Guangzhou 510630, China.
ACS Appl Mater Interfaces. 2017 Aug 9;9(31):25857-25869. doi: 10.1021/acsami.7b07167. Epub 2017 Jul 26.
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.
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。