TME-triggered MnSiO3@Met@GOx nanosystem for ATP dual-inhibited starvation/chemodynamic synergistic therapy

Zhang, Jiayao; Chen, Liang; Wei, Ziye; Yang, Wanlan; Ge, Wei; Qu, Xinyu; Si, Weili; Wang, Wenjun; Mou, Xiaozhou; Dong, Xiaochen

doi:10.1016/j.biomaterials.2022.121682

Cited by 25 publications

(12 citation statements)

References 32 publications

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“…Further studies have revealed that the tumor growth rate positively correlates with glucose levels and that high glucose levels in cancer patients are associated with poor prognosis [ 7 , 8 , 9 ]. Thus, cancer starvation therapy based on glucose deprivation is emerging as an effective treatment for suppressing tumor growth [ 10 , 11 , 12 ]. For example, the ketogenic diet can inhibit the metabolic proliferation of cancer cells by reducing blood glucose [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Zhang

Huang

et al. 2022

Cancers

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Reprogramming of glucose metabolism provides sufficient energy and raw materials for the proliferation, metastasis, and immune escape of cancer cells, which is enabled by glucose metabolism-related enzymes that are abundantly expressed in a broad range of cancers. Therefore, targeting glucose metabolism enzymes has emerged as a promising strategy for anticancer drug development. Although several glucose metabolism modulators have been approved for cancer treatment in recent years, some limitations exist, such as a short half-life, poor solubility, and numerous adverse effects. With the rapid development of medicinal chemicals, more advanced and effective glucose metabolism enzyme-targeted anticancer drugs have been developed. Additionally, several studies have found that some natural products can suppress cancer progression by regulating glucose metabolism enzymes. In this review, we summarize the mechanisms underlying the reprogramming of glucose metabolism and present enzymes that could serve as therapeutic targets. In addition, we systematically review the existing drugs targeting glucose metabolism enzymes, including small-molecule modulators and natural products. Finally, the opportunities and challenges for glucose metabolism enzyme-targeted anticancer drugs are also discussed. In conclusion, combining glucose metabolism modulators with conventional anticancer drugs may be a promising cancer treatment strategy.

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Section: Introductionmentioning

confidence: 99%

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Zhang

Huang

et al. 2022

Cancers

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“…[23] Studies increasingly show that glucose oxidase (GOx), a type of oxidoreductase, can decompose glucose and oxygen into gluconic acid and hydrogen peroxide (H 2 O 2 ). [24][25][26] Therefore, the covalent modification of GOx would yield starvation therapy against tumors, but also increase endogenous H 2 O 2 , thus amplifying the Fenton catalytic efficiency.…”

Section: Targeted Magnetic Resonance Imaging/near-infrared Dual-modal...mentioning

confidence: 99%

Targeted Magnetic Resonance Imaging/Near‐Infrared Dual‐Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

Guo

Ren

Chen

et al. 2023

Adv Funct Materials

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Accurate identification and visualization of peritoneal metastases (PM) are clinically essential to improving the prognosis for gastric cancer. However, owing to the multifocal spread of peritoneal metastasis nodules, small size, and close contact with adjacent organs, identifying and completely removing them during surgery is extremely challenging, resulting in cancer treatment failure and recurrence. This study develops a T1‐weighted magnetic resonance imaging (MRI) contrast agent (FeGdNP)‐loaded indocyanine green/glucose oxidase (ICG/GOx) with conjugation of an RGD dimer (RGD2) and acid‐labile polymer mPEG (FeGdNP‐ICG/GOx‐RGD2‐mPEG). Compared with commercial Magnevist, the proposed FeGdNP‐ICG/GOx‐RGD2‐mPEG shows a two to three‐fold higher tumor ΔSNR in MRI of peritoneal metastasis and subcutaneous animal models. Compared with free ICG, the increased fluorescent signal of FeGdNP‐ICG/GOx‐RGD2‐mPEG allows for the detection of tiny tumor metastatic nodules (<3 mm), and the removal of the peritoneum transplanted tumors. Abundant gluconic acid and H2O2 are generated during the GOx‐mediated glucose depletion process in cancer cells, thereby enhancing Fenton reaction efficiency. Accumulated toxic ·OH can damage the mitochondrial function and induce the release of mitochondrial reactive oxygen species, which activates the ferroptosis pathway. The data indicate the potential of the nanoparticles for MRI preoperative diagnosis, intraoperative fluorescence‐guided navigation, and ferroptosis tumor therapy.

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“…In case of insufficient glucose supply, tumor growth is significantly inhibited. Accordingly, starvation therapy relying on glucose consumption is a potential strategy for oncology treatment. − Glucose oxidase (GOx) has been reported to inhibit tumor growth by catalyzing the production of gluconic acid and hydrogen peroxide from glucose; it can thus be used to consume glucose and cut off the energy supply to tumor cells. − Moreover, hydrogen peroxide production by GOx can further improve the efficiency of CDT, providing a model of synergistic treatment. − In a previous study, a tumor-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT) was constructed by inserting glucose oxidase (GOx), catalase (CAT), and chlorinated e6 (Ce6) into human serum albumin (HSA) assembly molecules . Further, Fe 3 O 4 @ZIF-8/GOx@MnO 2 multilayered core–shell nanostructured hybrid nano-enzyme was studied for the synergistic treatment of multiple modalities .…”

Section: Introductionmentioning

confidence: 99%

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

Lai

Zheng³

et al. 2023

ACS Biomater. Sci. Eng.

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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.

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TME-triggered MnSiO3@Met@GOx nanosystem for ATP dual-inhibited starvation/chemodynamic synergistic therapy

Cited by 25 publications

References 32 publications

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Targeted Magnetic Resonance Imaging/Near‐Infrared Dual‐Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

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

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