Glucose oxidase-amplified CO generation for synergistic anticancer therapy via manganese carbonyl-caged MOFs.

Carbon monoxide (CO) as one of the therapeutic gaseous molecules has been widely applied for treating various diseases, especially in cancer therapy. However, the in situ-triggered and efficient transport of CO to tumors are the primary obstacles that limit its clinical applicability. To address this obstacle, herein, a H2O2-triggered CO gas releasing nanoplatform has been designed by embedding manganese carbonyl (MnCO) into Zr (IV)-based metal-organic frameworks (MOFs). The porous structures of MOFs provide encapsulation capacity for glucose oxidase (GOx) loading, thereby catalyzing the endogenous glucose into gluconic acid and H2O2 to accelerate CO release and energy depletion. In the meantime, the Mn2+ produced by MnCO can react with intracellular H2O2 via the Fenton reaction to form cytotoxic •OH. Therefore, the synthesized gas nanogenerator demonstrated a synergistic efficacy of CO gas therapy, reactive oxygen species (ROS)-mediated therapy, and energy starvation to prevent tumor growth. Both in vitro and in vivo studies indicated that this multifunctional nanoplatform not only successfully inhibited tumors through a synergistic effect, but also provided a new technique for the creation of starvation/gas/chemodynamic combination therapy in a single material. STATEMENT OF SIGNIFICANCE: In this study, we developed a H2O2 responsive CO gas nanogenerator to augment the in-situ generation of CO gas for combined modality therapy of tumors. The nanogenerator was constructed by encapsulating glucose oxidase (GOx) and manganese carbonyl (MnCO) into UiO-67-bpy, which can catalyze the conversion of intracellular glucose to H2O2 for cutting off energy supply of cancer cells. Meanwhile, the cumulated H2O2 can trigger the release of CO for gas therapy and generation of •OH for chemodynamic therapy (CDT) via the Fenton-like reaction, thereby resulting in apoptosis of the cancer cells. Collectively, our designed nanotherapeutic agent not only displays the synergistic therapy efficacy of starvation-enhanced CO gas therapy and CDT, but also provides an efficient strategy for developing the intelligent nanocarrier for CO gas delivery and release.

Glucose Oxidase Integrated Porphyrinic Covalent Organic Polymers for Combined Photodynamic/Chemodynamic/Starvation Therapy in Cancer Treatment.

The anticancer effect of photodynamic therapy (PDT) is usually impeded by the hypoxia microenvironment in solid tumors; thus, it requires integration with other treatment tactics to achieve an optimal anticancer efficacy. Porphyrin-containing nanotherapeutic agents are broadly used for PDT in tumor treatment. However, chemodynamic therapy (CDT) of porphyrin-based namomaterials has been rarely reported. Here, a novel nanoscale porphyrin-containing covalent organic polymer (PCOP) was designed by the cross-linking of 5,10,15,20-tetrakis(4-aminophenyl)porphyrin with 1,1'-ferrocenedicarboxylic acid at room temperature. After glucose oxidase (GOx) was loaded, the obtained nanotherapeutic agent of PCOPs@GOx presented an augmented synergy of PDT, CDT, and energy starvation to suppress tumor growth upon near-infrared light irradiation. In vitro and in vivo outcomes demonstrated that this multifunctional nanoplatform not only realized excellent tumor inhibition but also provided a new tactic for designing chemodynamic/photodynamic/starvation combined therapy in one material.

Rim-differentiated pillar[5]arene based nonporous adaptive crystals.

The first rim-differentiated pillar[5]arene based nonporous adaptive crystals (NACs) were developed and used to separate dichloromethane from a halomethane mixture with 99.1% purity.

GOx-assisted synthesis of pillar[5]arene based supramolecular polymeric nanoparticles for targeted/synergistic chemo-chemodynamic cancer therapy.

BACKGROUND: Cancer is the most serious world's health problems on the global level and various strategies have been developed for cancer therapy. Pillar[5]arene-based supramolecular therapeutic nano-platform (SP/GOx NPs) was constructed successfully via orthogonal dynamic covalent bonds and intermolecular H-bonds with the assistance of glucose oxidase (GOx) and exhibited efficient targeted/synergistic chemo-chemodynamic cancer therapy. METHODS: The morphology of SP/GOx NPs was characterized by DLS, TEM, SEM and EDS mapping. The cancer therapy efficinecy was investigated both in vivo and in vitro. RESULTS: SP/GOx NPs can load drug molecules (Dox) and modify target molecule (FA-Py) on its surface conveniently. When the resultant FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently, where GOx can catalyst the overexpressed glucose to generate H2O2. Subsequently, the generated H2O2 in cancer cells catalyzed by ferrocene unit to form •OH, which can kill cancer cells. Furthermore, the loaded Dox molecules released under acid microenvironment, which can further achieve chemo-therapy. CONCLUSION: All the experiments showed that the excellent antitumor performance of FA-Py/SP/GOx/Dox NPs, which provided an new method for pillar[5]arene-based supramolecular polymer for biomedical applications.