Development of a hypoxic nanocomposite containing high-Z element as 5-fluorouracil carrier activated self-amplified chemoradiotherapy co-enhancement

Development of a hypoxic nanocomposite containing high-Z element as 5-fluorouracil carrier activated self-amplified chemoradiotherapy co-enhancement
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开发含有高 Z 元素的缺氧纳米复合材料作为 5-氟尿嘧啶载体激活自放大放化疗协同增强

DOI:
10.1098/rsos.181790
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发表时间:
2019-06
影响因子:
3.5
通讯作者:
Hong Quan
Hong Quan
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cui Yang;Shan Peng;Yingming Sun;Hongtao Miao;Meng Lyu;Shijing Ma;Yuan Luo;Rui Xiong;Conghua Xie;Hong Quan

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化疗和放射治疗成果的协同效应令人鼓舞,但由于普遍存在低氧,导致实体肿瘤对药物/辐射产生抗药性,这一作用受到了严重制约。为了解决这一问题,提高癌症治疗的效率,本研究成功地设计并合成了甲硝唑(MI)、5-氟尿嘧啶(5-FU)和亚铁铂磁性纳米颗粒(MNPs)共输送的片状多功能氧化石墨烯(GO)给药系统,其平均粒径为243 nm。低氧药物载体同时负载放射增敏剂和化疗药物,在单个纳米平台内结合了低氧敏感性和放化疗协同增强的特性,有望为肿瘤的治疗提供新的思路。通过体外实验,证明了纳米复合材料的细胞内活性氧自由基(ROS)对低氧的敏感性和细胞毒性。此外,还揭示了MI、5-FU和FePT MNPs在细胞毒性和辐射增敏方面的相加效应。它增强了对细胞增殖的抑制,并组成了一个自我放大的放射治疗增强系统,同时提高了辐射效率和细胞的辐射敏感性。总之,这项研究推荐了一种新颖而有前景的多功能纳米平台,它具有自我放大效应,可以激活放化疗联合增强。
The synergetic effect of chemoradiotherapy achievement is encouraging but significantly hampered by the prevalence of hypoxia, leading to drug/radiation resistance in solid tumours. To address the problem and improve the efficiency of cancer therapy, a lamellar-structure multifunctional graphene oxide (GO) drug-delivery system with an average size of 243 nm, co-delivering of metronidazole (MI), 5-fluorouracil (5-FU) and FePt magnetic nanoparticles (MNPs), was successfully designed and synthesized in the study. The integration of hypoxic drug carrier loading radiosensitizers and chemotherapeutic drugs simultaneously, combines the properties of hypoxia-sensitivity and chemoradiotherapy co-enhancement within a single nanoplatform, which is expected to provide new ideas for cancer treatment. Through in vitro tests, the hypoxia-sensitivity and cytotoxicity of intracellular reactive oxygen species (ROS) of the nanocomposites (NCs) were proved. Moreover, the additive effect between MI, 5-FU and FePt MNPs in cytotoxicity and radiation sensitization aspects is disclosed. It performs an enhanced cell proliferation inhibition and makes up a self-amplified radiotherapy enhancement system that improves radiation efficiency and cell radiosensitivity simultaneously. In conclusion, the study recommended a novel and promising multifunctional nanoplatform which performed a self-amplified effect that activated chemoradiotherapy co-enhancement.
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