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肿瘤靶向白蛋白包被的硫化铋纳米颗粒(BiS)作为放射增敏剂和姜黄素载体用于增强放化疗

Tumor Targeted Albumin Coated Bismuth Sulfide Nanoparticles (BiS) as Radiosensitizers and Carriers of Curcumin for Enhanced Chemoradiation Therapy.

作者信息

Nosrati Hamed, Charmi Jalil, Salehiabar Marziyeh, Abhari Fatemeh, Danafar Hossein

机构信息

Department of pharmaceutical biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan 45139-56111, Iran.

Department of Physics, Faculty of Science, University of Zanjan, Zanjan 45371-38791, Iran.

出版信息

ACS Biomater Sci Eng. 2019 Sep 9;5(9):4416-4424. doi: 10.1021/acsbiomaterials.9b00489. Epub 2019 Aug 22.

DOI:10.1021/acsbiomaterials.9b00489
PMID:33438407
Abstract

Combination therapy such as radiotherapy combined with chemotherapy has attracted excessive interest in the new cancer research area. Therefore, developing nanobiomaterials for combination of radiotherapy and chemotherapy is required for more powerful and successful cures. Because of the amazing X-ray sensitization proficiency of Bi based nanoparticles, in this work, we synthesized and used BiS as an enhancer of X-ray radiation therapy, and furthermore, BiS served as carrier of curcumin (CUR), a chemotherapy drug, for the goal of combination therapy. Additionally, we selected and conjugated folic acid (FA) as a targeting molecule for the direction of the designed system to the tumor site. After characterization of drug loaded FA conjugated BiS@BSA nanoparticles (BiS@BSA-FA-CUR) and and safety assessment, we applied it for enhanced chemotherapy and X-ray radiation therapy in cancer cells and a tumor bearing mice model. Moreover, the CT contrast ability of synthesized nanoparticles was examined. Here, we (1) for the first time developed the novel and targeted CUR loaded BiS@BSA (BiS@BSA-FA-CUR) to promote chemoradiation therapy in 4T1 cells and breast tumor in mice; (2) found the synthesized nanoparticles to have good stability; (3) injected a single dose of the designed radiosensitizer for cancer therapy; and (4) used a conventional X-ray dose, 2Gy, for X-ray radiation therapy. The result of X-ray radiotherapy shows that the mice tumors vanished near 3 weeks after radiation. Interestingly, these results show that BiS@BSA-FA-CUR with the aid of X-ray can clearly promote the efficacy of chemoradiation therapy.

摘要

诸如放疗联合化疗的联合疗法在新的癌症研究领域引起了极大的关注。因此,开发用于放疗和化疗联合的纳米生物材料对于更有效且成功的治疗是必要的。由于铋基纳米颗粒具有惊人的X射线增敏能力,在本研究中,我们合成并使用BiS作为X射线放射治疗的增强剂,此外,BiS还作为化疗药物姜黄素(CUR)的载体,以实现联合治疗的目的。另外,我们选择并偶联叶酸(FA)作为靶向分子,将所设计的系统导向肿瘤部位。在对载药的FA偶联BiS@BSA纳米颗粒(BiS@BSA-FA-CUR)进行表征及安全性评估后,我们将其应用于癌细胞和荷瘤小鼠模型的增强化疗及X射线放射治疗。此外,还检测了合成纳米颗粒的CT造影能力。在此,我们(1)首次开发了新型靶向载CUR的BiS@BSA(BiS@BSA-FA-CUR)以促进4T1细胞和小鼠乳腺肿瘤的放化疗;(2)发现合成的纳米颗粒具有良好的稳定性;(3)注射单剂量的所设计的放射增敏剂用于癌症治疗;(4)使用2Gy的常规X射线剂量进行X射线放射治疗。X射线放疗结果显示,放疗后近3周小鼠肿瘤消失。有趣的是,这些结果表明BiS@BSA-FA-CUR借助X射线可明显提高放化疗疗效。

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