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超小钆基颗粒对肿瘤细胞的体外放射增敏作用。

In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

作者信息

Mowat P, Mignot A, Rima W, Lux F, Tillement O, Roulin C, Dutreix M, Bechet D, Huger S, Humbert L, Barberi-Heyob M, Aloy M T, Armandy E, Rodriguez-Lafrasse C, Le Duc G, Roux S, Perriat P

机构信息

LPCML, UMR 5620 CNRS, Université de Lyon, Université Claude Bernard, Bât. Berthollet, 2ème étage, 22 rue Gaston Berger 69622 Villeurbanne Cedex, France.

出版信息

J Nanosci Nanotechnol. 2011 Sep;11(9):7833-9. doi: 10.1166/jnn.2011.4725.

DOI:10.1166/jnn.2011.4725
PMID:22097494
Abstract

Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

摘要

由于放射疗法在癌症治疗中被广泛应用,开发既能降低辐射负担又能提高疗效,甚至在抗辐射肿瘤中也有效的策略至关重要。我们的新策略依赖于开发基于稀土(如钆)的固体混合纳米颗粒。在本文中,我们证实了基于钆的颗粒可以被设计成能够高效进入人胶质母细胞瘤细胞系U87,其进入量可通过改变孵育条件进行调节。这些尺寸小于5纳米的颗粒由氧化钆核心、聚硅氧烷外壳组成,并通过二乙烯三胺五乙酸(DTPA)进行功能化。尽管光电效应在[10 - 100 keV]范围内最大,但通过使用“单细胞凝胶电泳彗星试验”(一种测量辐射期间发生的DNA损伤数量的试验),发现此类颗粒在660 keV能量下具有高效的体外放射增敏特性。更有趣的是,通过MTT试验证明,对于2至8 Gy的剂量,这些颗粒在6 MeV能量下也是有效的放射增敏剂。基于钆的颗粒的特性为利用大多数医院已安装的辐射系统进行颗粒辅助放射治疗带来了有前景的开端。

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