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Improved synergic therapeutic effects of chemoradiation therapy with the aid of a co-drug-loaded nano-radiosensitizer under conventional-dose X-ray irradiation.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-06-26 , DOI: 10.1039/d0bm00353k
Hamed Nosrati 1 , Jalil Charmi , Fatemeh Abhari , Elahe Attari , Shayesteh Bochani , Behrooz Johari , Hamed Rezaeejam , Hamidreza Kheiri Manjili , Soodabeh Davaran , Hossein Danafar
Affiliation  

The goal of this work is to harness the advantages of a targeted hybrid nanostructure, BSA-coated Fe3O4 (F)-Au heterodimer, as a radiosensitizer and co-delivery vehicle of chemotherapeutic drugs for enhanced synergic cancer therapy and protection of healthy tissues. F-Au-BSA-MTX-CUR combines the abilities of enhanced X-ray radiation therapy (F-Au), long blood circulation time (BSA), tumor targeting (MTX), enhanced chemotherapy (MTX and CUR), and protection of normal cells against the harmful effects of radiation (CUR). In this work, we present the radioprotective and radiosensitizing effects of CUR on normal tissues and the tumor site, respectively. After technical evaluation, drug loading, drug release behavior, hemolysis assay, transfection efficacy, and cellular uptake studies with fluorescence microscopy, the biosafety and toxicity of the nanostructure was assessed in vitro and in vivo. Also, to confirm its power to improve synergistic chemoradiation therapy in mice, the antitumor effects of the designed treatment plan were assessed in a 4T1-tumor bearing mouse model. The in vivo antitumor effect evaluation interestingly reveals outstanding therapeutic power of the final formulation (F-Au-BSA-MTX-CUR) and further requirement of CUR as a radioprotective. This result importantly revealed the radioprotection effect of CUR. Co-delivery of the chemotherapeutic drugs MTX and CUR, combined with the radiosensitizing effect of the F-Au heterodimer and the radioprotective effect of CUR, showed promising prospects in cancer therapy.

中文翻译:

在常规剂量X射线辐照下,借助载药的纳米放射增敏剂,可提高化学放射疗法的协同治疗效果。

这项工作的目标是利用目标杂化纳米结构,BSA涂层的Fe 3 O 4的优势(F)-Au异二聚体,作为化学疗法药物的放射增敏剂和共同递送载体,用于增强协同癌症治疗和保护健康组织。F-Au-BSA-MTX-CUR结合了增强的X射线放射疗法(F-Au),较长的血液循环时间(BSA),肿瘤靶向(MTX),增强的化学疗法(MTX和CUR)以及以下方面的保护功能:正常细胞抵抗辐射的有害影响(CUR)。在这项工作中,我们介绍了CUR对正常组织和肿瘤部位的放射防护和放射增敏作用。经过技术评估,载药量,药物释放行为,溶血分析,转染功效和荧光显微镜下的细胞摄取研究后,在体外体内评估了纳米结构的生物安全性和毒性。同样,为了确认其改善小鼠协同化学放射治疗的能力,在载有4T1肿瘤的小鼠模型中评估了设计治疗方案的抗肿瘤作用。有趣的是,体内抗肿瘤作用评估显示了最终制剂(F-Au-BSA-MTX-CUR)的出色治疗能力,并进一步要求CUR作为放射防护剂。该结果重要地揭示了CUR的放射防护作用。化疗药物MTX和CUR的共同给药,与F-Au异二聚体的放射增敏作用和CUR的放射防护作用相结合,在癌症治疗中显示出广阔的前景。
更新日期:2020-07-28
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