金纳米颗粒放射增敏机制研究进展

Research Progress on Mechanisms Related to Radiosensitization of Gold Nanoparticles

金纳米颗粒(gold nanoparticles,GNPs)以其独特的理化特点而广泛应用于肿瘤诊疗研究。GNPs生物相容性好,原子序数高,对kV级射线的光电效应截面比软组织高,能提高肿瘤组织的局部能量沉积,是一种有良好应用前景的放射增敏剂。MV级射线通过康普顿散射与GNPs相互作用,但其截面远远低于kV级射线与GNPs作用的截面,因此GNPs对其增敏效应不如kV级射线显著。GNP诱导细胞内活性氧簇(reactive oxygen species,ROS)增加,引起DNA损伤,诱导细胞凋亡。GNPs通过调控细胞周期进程,使细胞阻滞在G_2/M期,增强细胞的放射敏感性。此外,GNPs还能引起细胞内自噬体增多和溶酶体降解能力减弱并最终引起细胞死亡。GNPs也可以抑制缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA表达,使裸鼠肝癌血管形态趋于正常。

Owing to its unique physicochemical properties,gold nanoparticles（GNPs） have been extensively used for cancer diagnosis and treatment. GNP is a high Z material with excellent biocompatibility,and its photoelectric cross section for low energy photon beams is larger compared to that of soft tissue,which makes it a promising radiation sensitizer. MV photon beams interact with GNPs dominantly through Compton scattering;the Compton scattering cross-section for MV photons is smaller than the photoelectric cross-section for keV photons,thus the radiosensitization effect is not as significant as that for kV photons. The radiosensitization of GNPs is implemented by increasing energy deposit in the surrounding cellular environment,elevating the level of reactive oxygen species,causing DNA damage and inducing cell apoptosis.GNPs can regulate cell cycle by arresting more cells in the G2/M phase,which is most sensitive to radiotherapy. Besides,GNPs induce autophagosome accumulation and lower the degradation capacity of lysosomes,eventually causing cell death. GNPs can also normalize vascellum by inhibiting HIF-1α mRNA and VEGF m RNA expression in hepatic tumor of nude mice.