A Three-in-one ZIFs-Derived CuCo(O)/GOx@PCNs Hybrid Cascade Nanozyme for Immunotherapy/Enhanced Starvation/Photothermal Therapy

Abstract

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 Cu0.3Co2.7O4 phase through X-ray diffraction analysis and it can react with H2O2 to generate O2 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.

pH-Regulating Nanoplatform for the “Double Channel Chase ” of Tumor Cells by the Synergistic Cascade between Chlorine Treatment and Methionine-Depletion Starvation Therapy

“…Furthermore, the survival status of 4T1 cells treated with those NPs was evaluated according to calceflavin AM (AM) and propidium iodide (PI) staining. 65 The control group showed significant green fluorescence, while the MFBC@CMR group showed intense red fluorescence, further verifying the damage of the MFBC@CMR NPs toward tumor cells (Figures 4d and S19). The same conclusion could be deduced by flow cytometric analysis (FCA) (Figures S20 and S21).…”

Research Progress on Improving the Efficiency of CDT by Exacerbating Tumor Acidification

“… 31–33 Glucose in TME will convert to gluconic acid and H 2 O 2 by introducing exogenous glucose oxidase (GOx), which is often used as one of the ways of tumor starvation therapy. 34 , 35 Among them, gluconic acid can provide appropriate acidic conditions for the Fenton reaction. Similarly, acidification can also further decompose the nano-delivery system and promote the cascade reaction.…”

“…In situ decomposition of H 2 O 2 into O 2 in tumor cells by catalase-active nanozymes is also an important strategy for reoxygenation. 35 A multi-functional nanoreactor Fe–MIL-88B–NH 2 @PFC-1-GOx (MPG), based on MOFs (Fe-MIL-88B-NH 2 ), hydrogen-bonded organic frameworks (PFC-1), and GOx, was reported by Hu. Here, the function of GOx was like the previous report.…”

Fenton/Fenton-like metal-based nanomaterials combine with oxidase for synergistic tumor therapy

“…Wang et al [ 17 ] synthesized Cu-doped cobalt oxide and porous carbon nanocomposites from bilayer ZIF-8@ZIF67 and further loaded them with GOx to get the CuCo(O)/GOx@PCNs hybrid nanozyme. CuCo(O) can react with H 2 O 2 to generate oxygen, relieving tumor hypoxia, restoring GOx enzymatic activity, further enhance starvation therapy.…”