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Ultrasmall theranostic nanozymes to modulate tumor hypoxia for augmenting photodynamic therapy and radiotherapy

机译：Utrorasmall Theranostic Nanozymes调节肿瘤缺氧以增加光动力治疗和放射疗法

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摘要

Photodynamic therapy (PDT) and radiotherapy (RT) are oxygen-dependent treatment strategies for solid tumors in clinics. However, the hypoxic tumor microenvironment induced by uncontrolled cancer cell proliferation significantly reduces the therapeutic efficacy of these strategies. Here, we rationally constructed indocyanine green (ICG)-loaded ultrasmall gold nanoclusters (Au NCs-ICG) as theranostic nanozymes for modulating tumor hypoxia and augmenting cancer PDT and RT, respectively. The constructed Au NC-ICG nanozymes with an ultrasmall particle size (similar to 1 nm) exhibited favorable renal clearance performance, high substrate affinity (K-m approximate to 2 mM) and good catalase-like activity (V-max approximate to 4.55 x 10(-3) mM s(-1)). In 4T1 tumor-bearing mouse models, high tumor accumulation of Au NC-ICG nanozymes was clearly visualized by near-infrared fluorescence, photoacoustic and computed tomography imaging, showing the potential for the monitoring and guidance of PDT and RT. In addition, the Au NCs-ICG nanozymes effectively decomposed intratumoral H2O2 into O-2 for overcoming hypoxia and subsequently enhancing PDT and RT, respectively. Moreover, the inherent X-ray absorption capacity of Au NCs-ICG greatly deposited radiation energy within the tumor region and further improved cancer RT. The integration of multimodal imaging, tumor hypoxia regulation, and effective therapy into ultrasmall Au NCs-ICG nanozymes shows great potential for cancer theranostic applications.
机译：光动力疗法（PDT）和放射疗法（RT）是诊所固体瘤的氧依赖处理策略。然而，由不受控制的癌细胞增殖引起的缺氧肿瘤微环境显着降低了这些策略的治疗效果。在此，我们将吲哚菁绿（ICG）制成 - 作为治疗纳米纳佐的吲哚菁绿（ICG）加载的超载纳米乳蛋白分别用于调节肿瘤缺氧和增强癌症PDT和RT。具有超粒子粒度（类似于1nm）的构建的Au NC-ICG纳佐表现出良好的肾间隙性能，高底物亲和力（Km近似至2mm）和良好的过氧化氢酶样活性（V-Max近似为4.55×10（ -3）mm s（-1））。在4T1携带的肿瘤小鼠模型中，通过近红外荧光，光声和计算机断层摄影成像清楚地可视化Au NC-ICG纳释的高肿瘤积累，显示PDT和室温的监测和指导的潜力。另外，Au NCS-ICG纳佐纳豆有效地分解肿瘤内的H2O2进入O-2以克服缺氧并随后增强PDT和室温。此外，AU NCS-ICG的固有X射线吸收能力大大沉积肿瘤区内的辐射能量，进一步改善癌症RT。多式联运成像，肿瘤缺氧调节和有效治疗进入超大使Au NCS-ICG纳米纳佐的整合表现出癌症治疗癌症的巨大潜力。

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  • 来源
    《Biomaterials Science》 |2020年第3期|共15页
  • 作者

    Dan Qing; Hu Dehong; Ge Yongshuai; Zhang Shiyu; Li Sanqing; Gao Duyang; Luo Wanxian; Ma Teng; Liu Xin; Zheng Hairong; Li Yingjia; Sheng Zonghai;

  • 作者单位

    Southern Med Univ Nanfang Hosp Dept Med Ultrason Guangzhou 510515 Peoples R China;

    Chinese Acad Sci Paul C Lauterbur Res Ctr Biomed Imaging Guangdong Prov Key Lab Nanomicro Mat Res Inst Biomed &

    Hlth Engn Shenzhen Inst Adv Technol Shenzhen 518055 Peoples R China;

    Chinese Acad Sci Paul C Lauterbur Res Ctr Biomed Imaging Guangdong Prov Key Lab Nanomicro Mat Res Inst Biomed &

    Hlth Engn Shenzhen Inst Adv Technol Shenzhen 518055 Peoples R China;

    Southern Med Univ Nanfang Hosp Dept Med Ultrason Guangzhou 510515 Peoples R China;

    Chinese Peoples Liberat Army Airborne Mil Hosp Wuhan 430012 Peoples R China;

    Chinese Acad Sci Paul C Lauterbur Res Ctr Biomed Imaging Guangdong Prov Key Lab Nanomicro Mat Res Inst Biomed &

    Hlth Engn Shenzhen Inst Adv Technol Shenzhen 518055 Peoples R China;

    Southern Med Univ Nanfang Hosp Dept Med Ultrason Guangzhou 510515 Peoples R China;

    Chinese Acad Sci Paul C Lauterbur Res Ctr Biomed Imaging Guangdong Prov Key Lab Nanomicro Mat Res Inst Biomed &

    Hlth Engn Shenzhen Inst Adv Technol Shenzhen 518055 Peoples R China;

    Chinese Acad Sci Paul C Lauterbur Res Ctr Biomed Imaging Guangdong Prov Key Lab Nanomicro Mat Res Inst Biomed &

    Hlth Engn Shenzhen Inst Adv Technol Shenzhen 518055 Peoples R China;

    Chinese Acad Sci Paul C Lauterbur Res Ctr Biomed Imaging Guangdong Prov Key Lab Nanomicro Mat Res Inst Biomed &

    Hlth Engn Shenzhen Inst Adv Technol Shenzhen 518055 Peoples R China;

    Southern Med Univ Nanfang Hosp Dept Med Ultrason Guangzhou 510515 Peoples R China;

    Chinese Acad Sci Paul C Lauterbur Res Ctr Biomed Imaging Guangdong Prov Key Lab Nanomicro Mat Res Inst Biomed &

    Hlth Engn Shenzhen Inst Adv Technol Shenzhen 518055 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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