Lysosome Targeting Chimaeras for Glut1-Facilitated Targeted Protein Degradation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(26), С. 17728 - 17737

Опубликована: Июнь 20, 2024

Targeted protein degradation technology holds great potential in biomedicine, particularly treating tumors and other protein-related diseases. Research on intracellular using molecular glues PROTAC is leading, while research the of membrane proteins extracellular through lysosomal pathway still preclinical stage. The scarcity useful targets an immense limitation to technological advancement, making it essential explore novel, potentially effective approaches for targeted degradation. Here, we employed glucose transporter Glut1 as innovative lysosome-targeting receptor devised Glut1-Facilitated Lysosomal Degradation (GFLD) strategy. We synthesized ligands via reversible addition-fragmentation chain transfer (RAFT) polymerization acquired antibody-glycooligomer conjugates bioorthogonal reactions molecules, utilized management PD-L1 high-expressing triple-negative breast cancer. a exhibits advancement broader array medications future.

Язык: Английский

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Selection of biofilm-inhibiting ssDNA aptamers against antibiotic-resistant Edwardsiella tarda by inhibition-SELEX and interaction with their binding proteins

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 140041 - 140041

Опубликована: Янв. 1, 2025

Язык: Английский

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Glut-1 inhibition in breast cancer cells

Vitamins and hormones, Год журнала: 2025, Номер unknown, С. 181 - 211

Опубликована: Янв. 1, 2025

Язык: Английский

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Regulatory T Cell Metabolism: A Promising Therapeutic Target for Cancer Treatment?

Immune Network, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 1, 2025

Regulatory T (Treg) cells are essential for maintaining immune homeostasis by suppressing excessive responses. In the context of cancer, however, Tregs promote evasion and tumor progression, particularly through their unique adaptations within microenvironment (TME). Recent research has emphasized how metabolic characteristics shape Treg activation, migration, immunosuppressive function, revealing impact pathways on fitness in TME. this review, we first provide an overview cancer immunology, discussing roles properties specific to We then examine requirements activation migration under normal conditions, followed a discussion hypoxia, lactate accumulation, nutrient limitation, oxidative stress, other TME-specific factors alter metabolism contribute evasion. Finally, explore therapeutic strategies that target TME, including pharmacological modulation diminish Treg-mediated immunosuppression. Thus, could suggest future directions clinical implications Treg-targeted as complementary approach treatment, setting stage novel immunotherapy.

Язык: Английский

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Enhancing immunotherapy with tumour-responsive nanomaterials

Nature Reviews Clinical Oncology, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Язык: Английский

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Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy

Experimental Hematology and Oncology, Год журнала: 2025, Номер 14(1)

Опубликована: Март 14, 2025

Abstract Immunotherapy targeting immune checkpoints has gained traction across various cancer types in clinical settings due to its notable advantages. Despite this, the overall response rates among patients remain modest, alongside issues of drug resistance and adverse effects. Hence, there is a pressing need enhance checkpoint blockade (ICB) therapies. Post-translational modifications (PTMs) are crucial for protein functionality. Recent research emphasizes their pivotal role regulation, directly impacting expression function these key proteins. This review delves into influence significant PTMs—ubiquitination, phosphorylation, glycosylation—on signaling. By modifications, novel immunotherapeutic strategies have emerged, paving way advancements optimizing therapies future.

Язык: Английский

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Reprogramming of Glucose Metabolism by Nanocarriers to Improve Cancer Immunotherapy: Recent Advances and Applications

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 4201 - 4234

Опубликована: Апрель 1, 2025

Although immunotherapy has made significant progress in cancer treatment, its limited responsiveness greatly hindered widespread clinical application. The Warburg effect tumor cells creates a microenvironment (TME) characterized by hypoxia, low glucose levels, and high lactate which severely inhibits the antitumor immune response. Consequently, targeting metabolism to reprogram TME is considered an effective strategy for reversing immunosuppression evasion. Numerous studies have been conducted on enhancing efficacy through delivery of modulators via nanocarriers. This review provides comprehensive overview metabolic characteristics tumors their impacts system, as well nanodelivery strategies enhance immunotherapy. These include inhibiting key glycolytic enzymes, blocking transporters, utilizing oxidase oxidase. Furthermore, this article reviews recent advancements synergistic therapy involving metabolism-targeted combined with other treatments, such chemotherapy, radiotherapy (RT), phototherapy, Finally, we discuss limitations future prospects nanotechnology therapy, hoping provide new directions ideas improve

Язык: Английский

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Identification of Rapaglutin E as an Isoform-Specific Inhibitor of Glucose Transporter 1

ACS Chemical Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Natural products rapamycin and FK506 are macrocyclic compounds with therapeutic benefits whose unique scaffold inspired the generation exploration of hybrid macrocycle rapafucins. From this library, a potent inhibitor facilitative glucose transporter (GLUT), rapaglutin A (RgA), was previously identified. RgA is pan-GLUT Class I isoforms GLUT1, GLUT3, GLUT4. Herein, we report discovery E (RgE). Unlike RgA, RgE highly specific for GLUT1. Further characterization revealed that likely bound to distinct sites on GLUT1 despite their shared FKBP-binding domain, suggesting effector domains play key roles in recognition GLUTs.

Язык: Английский

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Pt–PtTe₂ Nanoparticles with Heterojunction-Based Accelerated Electron Transfer for Efficient Tumor Therapy

ACS Applied Nano Materials, Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

Язык: Английский

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Mannose modified graphene oxide drug-delivery system targets cancer stem cells and tumor-associated macrophages to promote immunotherapeutic efficacy

Colloids and Surfaces B Biointerfaces, Год журнала: 2025, Номер unknown, С. 114710 - 114710

Опубликована: Апрель 1, 2025

Язык: Английский

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