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恶性肿瘤是目前世界上致死率较高的一类疾病。目前临床上对于肿瘤的治疗方式主要分为3大类:手术治疗、放疗及化疗。放疗通常分外照射治疗(external beam radiotherapy,EBRT)和内部放射性同位素治疗。通常患者会选择单独治疗或两种及两种以上的治疗方式联合治疗[1]。但是,这些治疗方式的治疗效果并不尽如人意,在过去的几十年中,患者的生存率并没有显著升高。肿瘤的发生存在多种机制,不同肿瘤的发生机制可能存在差异,同一种肿瘤在不同个体间的发生和治疗效果也不尽相同。据统计,国内有60%~70%的肿瘤患者选择放疗,但只有40%左右的患者被治愈[2]。放疗过程中软组织吸收的能量很少,在高密度组织的放疗中,射线对周围正常组织的辐射损伤比较大[3-4],实体瘤内部乏氧环境使其对射线不敏感,从而导致放疗效果不理想。放疗增敏剂的出现提高了放疗效率,同时也减轻了放疗对正常组织的辐射损伤,其作用原理是缺氧的肿瘤微环境在放疗后产生的水化电子(eaq-)能够被一些高亲电子制剂氧化并迅速清除[1]。目前临床上常用的上述放疗增敏剂是硝基咪唑类或硝基苯衍生物,此类药物因其本身化学结构的特殊性,注射入人体后会产生神经毒性和生殖毒性,对机体产生极大的不良反应,从而限制了其临床应用[5-6]。近年来,硝基咪唑类衍生物不断被研制出来并用于放疗增敏的研究中,但仍旧存在着毒性大等问题。甘氨双唑钠是目前已经在临床上使用的放疗增敏剂,但它的不良反应目前仍旧无法彻底解决[7]。
随着纳米医学的快速发展,人们对使用纳米材料或纳米载体提高肿瘤对放疗的敏感性产生了很大兴趣[8]。能够吸收放射性射线的纳米材料在放疗期间可作为放疗增敏剂通过增强渗透滞留效应靶向到达肿瘤组织,在肿瘤内吸收射线并通过光电效应和康普顿效应放大辐射能量,进而提高放疗效果。高原子序数纳米材料金纳米粒子(gold nanoparticles, GNPs)能够吸收大量的X射线,同时,作为放射源,GNPs能够产生并释放出不同类型的射线[9]。释放出的射线根据其各自的物理特性产生高性能电离效应,进而将辐射能量集中在肿瘤内,从而提高放疗的抗肿瘤效果。同时,由于GNPs有近红外吸收的特性,因此可将其用于肿瘤的光热治疗中,放疗和光热联合治疗可以进一步提高肿瘤的治疗效果[10]。
金纳米粒子在肿瘤放疗中的研究进展
Advances in the application of gold nanoparticles in tumor radiotherapy
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摘要: 放疗在肿瘤的治疗中起着不可替代的作用,但由放疗引起的不良反应以及放疗过程中的肿瘤耐受问题仍未得到根本解决,因此放疗增敏显得尤为重要。金纳米粒子(GNPs)作为新型的纳米类放疗增敏制剂,因其较高的生物相容性受到了专家学者的广泛关注和研究。作为新型的纳米制剂,GNPs的理化性质,包括粒径、表面电荷和组装形态等能够影响体内代谢行为和肿瘤蓄积,因此导致放疗增敏率不同。笔者对近几年GNPs作为放疗增敏制剂的研究进展做进一步的总结和进展性汇报。Abstract: Even though radiotherapy plays an important role in the treatment of tumors, the problems of toxic and side effects of normal tissues produced by radiotherapy and tumor tolerance to irradiation have not been solved. Gold nanoparticles(GNPs) are a new type of nanoparticle radiosensitizer. As a radiosensitizer, GNPs have become the focus of research because of their high biocompatibility. Their physical and chemical properties(including size, surface charge, and shape) can affect their metabolism behavior and tumor accumulation, thereby resulting in different sensitizing effect of radiotherapy. This review will summarize the progress of recent research on GNPs as a radiosensitizer.
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Key words:
- Nanoparticles /
- Gold /
- Neoplasms /
- Radiotherapy /
- Sensitization
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