我铋纳米颗粒提供肿瘤微环境敏感的前药以增强肿瘤特异性光放射治疗

铋纳米颗粒提供肿瘤微环境敏感的前药以增强肿瘤特异性光放射治疗

作者：小柯机器人 发布时间：2021/7/25 1:03:17

本期文章：《美国化学会志》：Online/在线发表

中国科学院高能物理研究所晏亮团队报道了高度稳定的二氧化硅包裹的铋纳米颗粒，提供肿瘤微环境敏感的前药以增强肿瘤特异性光放射治疗。相关研究成果于2021年7月22日发表在国际顶尖学术期刊《美国化学会杂志》。

放射增敏剂是一种能够通过增强DNA损伤和增强自由基氧物种（ROS）生成来增强肿瘤组织损伤的药物。然而，这种放射增敏剂在临床上的应用仍然受到限制，因为它不能区分癌细胞和正常细胞，而且还存在一种可逆的谷胱甘肽系统，可以减少ROS的生成量。

该文中，为了解决这些限制，研究人员设计了一种H2O2响应的前药，可以与月桂酸（熔点～43℃）预混合，并装载在二氧化硅包裹的铋纳米颗粒（BSNP）表面周围，用于癌症特异性光放射治疗。特别是，二氧化硅涂层赋予BSNP更好的抗近红外光和X射线的化学稳定性。在光热加热时，月桂酸熔化以触发前药释放，随后通过H2O2刺激转化为对醌甲酰胺以不可逆地烷基化谷胱甘肽。同时，这种热量促进肿瘤氧合，帮助缓解缺氧的微环境。经X射线连续照射后，BSNPs产生大量的ROS，与这些事件联合作用，通过DNA断裂和线粒体介导的凋亡途径协同诱导细胞死亡，最终有效抑制体内肿瘤生长，具有较高的肿瘤特异性，并减少副作用。

总的来说，该工作提出了一个有潜力的方法来改善其他活性氧反应的前烷基化剂，同时强调了一个强大的纳米系统，用于将这些前药与光放射增敏剂相结合，以实现精确的光放射治疗。

附：英文原文

Title: Highly Stable Silica-Coated Bismuth Nanoparticles Deliver Tumor Microenvironment-Responsive Prodrugs to Enhance Tumor-Specific Photoradiotherapy

Author: Huandong Xiang, Yuanzheng Wu, Xianyu Zhu, Mengyao She, Qi An, Ruyi Zhou, Peng Xu, Feng Zhao, Liang Yan, Yuliang Zhao

Issue&Volume: July 22, 2021

Abstract: Radiosensitizers are agents capable of amplifying injury to tumor tissues by enhancing DNA damage and fortifying production of radical oxygen species (ROS). The use of such radiosensitizers in the clinic, however, remains limited by an insufficient ability to differentiate between cancer and normal cells and by the presence of a reversible glutathione system that can diminish the amount of ROS generated. Here, to address these limitations, we design an H2O2-responsive prodrug which can be premixed with lauric acid (melting point ～43 °C) and loaded around the surface of silica-coated bismuth nanoparticles (BSNPs) for cancer-specific photoradiotherapy. Particularly, silica coating confers BSNPs with improved chemical stability against both near-infrared light and X-rays. Upon photothermal heating, lauric acid is melted to trigger prodrug release, followed by its transformation into p-quinone methide via H2O2 stimulation to irreversibly alkylate glutathione. Concurrently, this heat boosts tumor oxygenation and helps relieve the hypoxic microenvironment. Following sequential irradiation by X-rays, BSNPs generate plentiful ROS, which act in combination with these events to synergistically induce cell death via DNA breakage and mitochondria-mediated apoptosis pathways, ultimately enabling effective inhibition of tumor growth in vivo with high tumor specificity and reduced side effects. Collectively, this work presents a promising approach for the improvement of other ROS-responsive proalkylating agents, while simultaneously highlighting a robust nanosystem for combining these prodrugs with photoradiosensitizers to realize precision photoradiotherapy.

DOI: 10.1021/jacs.1c03303

Source: https://pubs.acs.org/doi/10.1021/jacs.1c03303

期刊信息

JACS：《美国化学会志》，创刊于1879年。隶属于美国化学会，最新IF：14.612

官方网址：https://pubs.acs.org/journal/jacsat

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