Dual-Functional Nanoplatform Based on Bimetallic Metal–Organic Frameworks for Synergistic Starvation and Chemodynamic Therapy

Abstract

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) mediated by nanozymes has been extensively studied in oral squamous cell carcinoma. However, the low catalytic efficiency due to insufficient H2O2 in the TME is still a major challenge for its clinical translation. Herein, we present an antitumor nanoplatform based on a Mn–Co organometallic framework material (MnCoMOF), which shows peroxidase-like (POD-like) activity, loaded with glucose oxidase (GOx@MnCoMOF), demonstrating the ability of H2O2 self-supply and H2O2 conversion to toxic hydroxyl radicals. The encapsulated GOx efficiently catalyzes glucose into gluconic acid and H2O2 at the tumor site, which can cut off the energy supply to inhibit tumor growth and produce a large amount of H2O2 and acid to compensate for their lack in the tumor microenvironment. The POD-like activity of MnCoMOF can convert H2O2 into hydroxyl radicals and eliminate tumor cells. The nanoplatform exhibits enhanced tumor cell cytotoxicity in a high-glucose medium compared with a low-glucose medium, illustrating sufficient generation of H2O2 from glucose by GOx. The in vivo results indicate that GOx@MnCoMOF has excellent antitumor efficacy and can remodel the immune-suppressive tumor microenvironment. In conclusion, the GOx@MnCoMOF nanoplatform possesses dual enzymatic activities, i.e., POD-like and glucose oxidase, to achieve improved tumor-suppressive efficiency through synergistic starvation and chemodynamic therapy, thus providing a new strategy for the clinical treatment of oral cancer.

The applications of nanozymes in cancer therapy: based on regulating pyroptosis, ferroptosis and autophagy of tumor cells

“…GOx@MnCoMOF nanozyme achieves higher antitumor effect through dual enzyme activity, synergistic starvation and chemodynamic therapy. 51…”

CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy

“…Cancer cells cultivate a unique tumor microenvironment (TME) marked by pronounced acidity and hypoxia, stemming from their increased metabolic needs and an acute dependency on the steady influx of glucose to foster rapid growth. − The progression of nanomedicine has opened up new opportunities for cancer treatment, with nanocatalytic therapy assuming a prominent position. , This approach primarily involves a chemical reaction in situ within the tumor, employing catalytically active nanomaterials to produce toxic substances for targeting and eliminating tumor cells. To effectively leverage these TME attributes, considerable research endeavors have focused on the advancement of efficacious and low-toxicity nanocatalytic treatments leveraging TME characteristics. − However, the intrinsic hypoxic conditions within the tumors substantially limit the effectiveness of photodynamic therapy (PDT), thereby fortifying tumor proliferation and metastasis. − Notwithstanding numerous attempts such as deploying nanoparticles bearing catalase (CAT)-like activity to transmute hydrogen peroxide (H 2 O 2 ) into oxygen (O 2 ) to neutralize tumor cell hypoxia, the outcomes have been suboptimal due to the scant endogenous H 2 O 2 availability within tumors. − Concomitantly, endogenous H 2 O 2 proves insufficient for sustained reactive oxygen species (ROS) production. − As a result, the development of a chemical reaction in situ system, custom-tailored to a TME, is critically essential for establishing a robust platform to regulate the levels of H 2 O 2 , O 2 , and glucose, ultimately contributing to the inhibition of tumor cell proliferation.…”

System Xc− exacerbates metabolic stress under glucose depletion in oral squamous cell carcinoma

“…These nanoparticles deplete extracellular glucose and promote H 2 O 2 production, mimicking glucose starvation and a Fenton-like reaction (Fu et al, 2018(Fu et al, , 2019. The potential use of GOx nanoparticles in the clinical treatment of OSCC was recently confirmed (Xiao et al, 2023). System Xc − is composed of a substrate-specific subunit xCT/ SLC7A11 and a regulatory subunit CD98/SLC3A2.…”