Tumor Microenvironment-Activated Theranostics Nanozymes for Fluorescence Imaging and Enhanced Chemo-Chemodynamic Therapy of Tumors

Abstract

Chemodynamic therapy (CDT) is widely explored for tumor-specific therapy by converting endogenous H 2 O 2 to lethal •OH to destroy cancer cells. However, •OH scavenging by glutathione (GSH) and insufficient intratumoral H 2 O 2 levels seriously hinder the application of CDT. Herein, we reported the fabrication of copper ion-doped ZIF-8 loaded with gold nanozymes and doxorubicin hydrochloride (DOX) for the chemotherapy and CDT synergistic treatment of tumors with the assistance of tumor microenvironment (TME)-activated fluorescence imaging. The Cu 2+ -doped ZIF-8 shell was gradually degraded to release DOX and gold nanoclusters responding to the acidic TME. The fluorescence signal of the tumor region was acquired after the quenched fluorescence of the gold nanoclusters by Cu 2+ and DOX by aggregation-induced quenching was turned on because of the interaction of GSH with Cu 2+ and the release of free DOX. The Cu 2+ ions could deplete the GSH via redox reactions and the generated Cu + could convert internal H 2 O 2 to •OH for tumor CDT. The chemotherapeutic effect of DOX was strengthened through drug efflux inhibition and drug sensitivity increase due to the consumption of GSH and •OH burst. Moreover, DOX could raise the level of H 2 O 2 and augment the effect of CDT. In addition, the fluorescent gold nanoclusters not only served as a peroxidase to convert H 2 O 2 to •OH but also employed as an oxidase to consume GSH, resulting in the amplification of chemotherapy and CDT. This work presents an approach to construct tumor microenvironment-activated theranostic probes without external stimuli and to achieve the tumor elimination through cascade reactions and synergistic treatment.

Fluorescence-Reporting-Guided Tumor Acidic Environment-Activated Triple Photodynamic, Chemodynamic, and Chemotherapeutic Reactions for Efficient Hepatocellular Carcinoma Cell Ablation

“…To further investigate whether SPFT shows tumor-specific cytotoxicity, we selected HELF normal cells as the control cell lines to compare with HepG2 cells (Figure C,D). As reported, compared with normal tissues and cells, lower pH and higher H 2 O 2 are the two of the important characteristics of tumor tissues and cells. , As shown in Figure C, higher cytotoxicity of SPFT toward HepG2 cells than that toward HELF cells is observed in the dark. This result is attributed to the slightly acidic environment in tumor cells, which can destroy the Fe III -TA shell and then trigger chemodynamic therapy and chemotherapy.…”

Metal–Organic Frameworks-Mediated Assembly of Gold Nanoclusters for Sensing Applications

“…These outstanding performances of MOF/AuNCs assemblies facilitate the sensitive colorimetric sensing of organophosphorus pesticides (OPs), acetylcholinesterase (AChE), choline oxidase (CHO), glucose, hydrogen peroxide, etc. [ 70 , 71 , 121 – 123 ].…”

Bioresponsive Nanomaterials: Recent Advances in Cancer Multimodal Imaging and Imaging-Guided Therapy

“…Chemodynamic therapy is a specific tumor treatment and can make tumor cells sensitive to chemotherapy drugs thus improving the chemo therapy effect (Wang et al,2018). Recent study indicated that a novel theranostics nanozymes can be used for both fluorescence imaging and enhancing chemo-chemodynamic therapy (Figure 6) (Zhao et al,2021).…”