Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province , Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences , Ningbo 315201 , P. R. China.
University of Chinese Academy of Sciences , Beijing 100049 , P. R. China.
Nano Lett. 2019 Aug 14;19(8):5674-5682. doi: 10.1021/acs.nanolett.9b02253. Epub 2019 Aug 1.
The efficiency of chemical intercommunication between enzymes in natural networks can be significantly enhanced by the organized catalytic cascades. Nevertheless, the exploration of two-or-more-enzymes-engineered nanoreactors for catalytic cascades remains a great challenge in cancer therapy because of the inherent drawbacks of natural enzymes. Here, encouraged by the catalytic activity of the individual nanozyme for benefiting the treatment of solid tumors, we propose an organized in situ catalytic cascades-enhanced synergistic therapeutic strategy driven by dual-nanozymes-engineered porphyrin metal-organic frameworks (PCN). Precisely, catalase-mimicking platinum nanoparticles (Pt NPs) were sandwiched by PCN, followed by embedding glucose oxidase-mimicking ultrasmall gold nanoparticles (Au NPs) within the outer shell, and further coordination with folic acid (P@Pt@P-Au-FA). The Pt NPs effectively enabled tumor hypoxia relief by catalyzing the intratumoral HO to O for (1) enhancing the O-dependent photodynamic therapy and (2) subsequently accelerating the depletion of β-d-glucose by Au NPs for synergistic starving-like therapy with the self-produced HO as the substrate for Pt NPs. Consequently, a remarkably strengthened antitumor efficiency with prevention of tumor recurrence and metastasis was achieved. This work highlights a rationally designed tumor microenvironment-specific nanoreactor for opening improved research in nanozymes and provides a means to design a catalytic cascade model for practical applications.
在自然网络中，酶之间的化学通讯效率可以通过有组织的催化级联得到显著提高。然而，由于天然酶固有的缺陷，探索用于催化级联的两种或更多酶工程纳米反应器在癌症治疗中仍然是一个巨大的挑战。在这里，受单个纳米酶催化活性有益于实体瘤治疗的启发，我们提出了一种由双纳米酶工程卟啉金属-有机骨架（PCN）驱动的原位催化级联增强协同治疗策略。具体来说，模拟过氧化物酶的铂纳米粒子（Pt NPs）被 PCN 夹在中间，然后在外壳内嵌入模拟葡萄糖氧化酶的超小金纳米粒子（Au NPs），并进一步与叶酸（P@Pt@P-Au-FA）配位。Pt NPs 通过催化肿瘤内的 HO 到 O 反应（1）增强 O 依赖性光动力治疗，（2）随后加速 Au NPs 消耗 β-d-葡萄糖，从而利用自身产生的 HO 作为 Pt NPs 的底物进行协同饥饿样治疗，有效地缓解了肿瘤缺氧。因此，实现了抗肿瘤效率的显著增强，防止了肿瘤的复发和转移。这项工作突出了一种合理设计的肿瘤微环境特异性纳米反应器，为改进纳米酶的研究开辟了道路，并为实际应用设计催化级联模型提供了一种手段。
