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 (∼1 nm) exhibited favorable renal clearance performance, high substrate affinity (Km≈ 2 mM) and good catalase-like activity (Vmax≈ 4.55 × 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 O2 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.

中文翻译：

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超小型治疗神经纳米酶可调节肿瘤缺氧，增强光动力疗法和放射疗法。

光动力疗法（PDT）和放射疗法（RT）是临床上针对实体瘤的氧依赖性治疗策略。然而，由不受控制的癌细胞增殖诱导的低氧肿瘤微环境显着降低了这些策略的治疗功效。在这里，我们合理地构建了装载吲哚菁绿（ICG）的超小金纳米簇（Au NCs-ICG）作为治疗肿瘤纳米酶，分别用于调节肿瘤缺氧和增强癌症PDT和RT。构建的具有超小粒径（〜1 nm）的Au NC-ICG纳米酶表现出良好的肾脏清除性能，高底物亲和力（Km≈2 mM）和良好的过氧化氢酶样活性（Vmax≈4.55×10-3 mM s-1 ）。在带有4T1肿瘤的小鼠模型中，通过近红外荧光可以清楚地看到Au NC-ICG纳米酶在肿瘤中的大量积累，光声和计算机断层摄影成像，显示了监测和指导PDT和RT的潜力。另外，Au NCs-ICG纳米酶有效地将肿瘤内的H2O2分解为O2，以克服缺氧并随后分别增强PDT和RT。此外，Au NCs-ICG固有的X射线吸收能力极大地在肿瘤区域内沉积了辐射能，并进一步改善了癌症放疗。将多模式成像，肿瘤缺氧调节和有效疗法整合到超小型Au NCs-ICG纳米酶中，显示出在癌症治疗学应用中的巨大潜力。Au NCs-ICG纳米酶有效地将肿瘤内的H2O2分解为O2，以克服缺氧并随后分别增强PDT和RT。此外，Au NCs-ICG固有的X射线吸收能力极大地在肿瘤区域内沉积了辐射能，并进一步改善了癌症放疗。将多模式成像，肿瘤缺氧调节和有效疗法整合到超小型Au NCs-ICG纳米酶中，显示出在癌症治疗学应用中的巨大潜力。Au NCs-ICG纳米酶有效地将肿瘤内的H2O2分解为O2，以克服缺氧并随后分别增强PDT和RT。此外，Au NCs-ICG固有的X射线吸收能力极大地在肿瘤区域内沉积了辐射能，并进一步改善了癌症放疗。将多模式成像，肿瘤缺氧调节和有效疗法整合到超小型Au NCs-ICG纳米酶中，显示出在癌症治疗学应用中的巨大潜力。