College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, China.
Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, 59 Haier Road, Qingdao, Shandong 266071, China.
ACS Appl Mater Interfaces. 2021 Mar 17;13(10):11683-11695. doi: 10.1021/acsami.1c01006. Epub 2021 Mar 3.
Glucose oxidase (GOx) is regarded as an ideal endogenous natural enzyme for tumor starvation therapy and photothermal therapy (PTT) is a promising strategy for the ablation of primary tumor. In this work, Cu-doped cobalt oxide and porous carbon nanocomposites (CuCo(O)@PCNs) were synthesized from double-layered ZIF-8@ZIF-67 and GOx was loaded in the porous carbon to form a CuCo(O)/GOx@PCNs hybrid nanozyme. CuCo(O) was characterized as the CuCoO phase through X-ray diffraction analysis and it can react with HO to generate O and alleviate tumor hypoxia, resulting in the recovered enzymatic activity of GOx and the enhanced starvation therapy. The porous nanocarbon can ablate the primary tumor because of its high photothermal conversion efficiency of 40.04%. The three-in-one functions of oxygen supply, glucose consumption, and photothermal conversion were realized in the ZIFs-derived CuCo(O)/GOx@PCNs nanozyme and the starvation therapy effect was improved by PTT and oxygen supplement. Furthermore, the inhibition effect of CuCo(O)/GOx@PCNs on metastatic tumor is similar to combined therapy of the nanozyme and the immune checkpoint-blocking antibody, α-PD-1. The related antitumor immune mechanism was studied through the analysis of immune-related proinflammatory cytokines and the activated T cells. This work may provide new ideas for the development and application of the ZIFs-derived hybrid nanozyme in tumor therapy and the CuCo(O)/GOx@PCNs nanozyme may be a promising alternative to immune checkpoint inhibitors.
葡萄糖氧化酶（GOx）被认为是肿瘤饥饿治疗的理想内源性天然酶，光热治疗（PTT）是消融原发性肿瘤的一种很有前途的策略。在这项工作中，从双层 ZIF-8@ZIF-67 合成了铜掺杂的氧化钴和多孔碳纳米复合材料（CuCo(O)@PCNs），并将 GOx 负载在多孔碳中形成 CuCo(O)/GOx@PCNs 杂化纳米酶。通过 X 射线衍射分析，CuCo(O) 被表征为 CuCoO 相，它可以与 HO 反应生成 O，缓解肿瘤缺氧，从而恢复 GOx 的酶活性并增强饥饿治疗效果。多孔纳米碳由于其 40.04%的高光热转换效率，可以消融原发性肿瘤。在 ZIFs 衍生的 CuCo(O)/GOx@PCNs 纳米酶中实现了供氧、消耗葡萄糖和光热转换的三种功能，通过 PTT 和供氧提高了饥饿治疗效果。此外，CuCo(O)/GOx@PCNs 对转移性肿瘤的抑制作用与纳米酶和免疫检查点阻断抗体α-PD-1 的联合治疗相似。通过分析免疫相关促炎细胞因子和激活的 T 细胞，研究了相关的抗肿瘤免疫机制。这项工作可能为 ZIFs 衍生的杂交纳米酶在肿瘤治疗中的开发和应用提供新的思路，CuCo(O)/GOx@PCNs 纳米酶可能是免疫检查点抑制剂的一种有前途的替代品。
