Metabolism, metabolites, and macrophages in cancer

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: July 25, 2023

Abstract Tumour-associated macrophages (TAMs) are crucial components of the tumour microenvironment and play a significant role in development drug resistance by creating an immunosuppressive microenvironment. Macrophages essential both innate adaptive immune systems contribute to pathogen regulation organism homeostasis. Macrophage function polarization closely linked altered metabolism. Generally, M1 rely primarily on aerobic glycolysis, whereas M2 depend oxidative Metabolic studies have revealed that metabolic signature TAMs metabolites regulate TAMs. However, precise effects reprogramming tumours remain incompletely understood. In this review, we discuss impact pathways macrophage as well potential strategies for metabolism cancer treatment.

Language: Английский

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Microenvironment-Responsive Metal-Phenolic Nanozyme Release Platform with Antibacterial, ROS Scavenging, and Osteogenesis for Periodontitis

ACS Nano, Journal Year: 2023, Volume and Issue: 17(19), P. 18732 - 18746

Published: Sept. 28, 2023

Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in destruction periodontal tissues. At present, main therapeutic modalities, such as local mechanical debridement antibiotic delivery, are not only difficult to solve intractable bacterial biofilm effectively but also tricky ameliorate response well regenerate impaired Herein, we have proposed TM/BHT/CuTA hydrogel system formed self-assembly copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged can retain at inflammation sites with positive charge through electrostatic adsorption hydrolyze increasing MMP periodontitis, realizing on-demand release nanozyme. released has antibacterial antiplaque properties. Meanwhile, metal-phenolic nanozyme, it scavenge multiple ROS simulating cascade process superoxide dismutase (SOD) catalase (CAT). Further, modulate macrophage polarization M1 phenotype M2 Nrf2/NF-κB pathway, which reduces pro-inflammatory cytokines, increases anti-inflammatory promotes expression osteogenetic genes successively, thus relieving accelerating tissue regeneration periodontitis. Altogether, this multifunctional platform (TM/BHT/CuTA) provides desirable strategy for treatment

Language: Английский

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Modular-designed engineered bacteria for precision tumor immunotherapy via spatiotemporal manipulation by magnetic field

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 23, 2023

Abstract Micro-nano biorobots based on bacteria have demonstrated great potential for tumor diagnosis and treatment. The bacterial gene expression drug release should be spatiotemporally controlled to avoid in healthy tissues undesired toxicity. Herein, we describe an alternating magnetic field-manipulated tumor-homing developed by genetically modifying engineered Escherichia coli with Fe 3 O 4 @lipid nanocomposites. After accumulating orthotopic colon tumors female mice, the paramagnetic nanoparticles enable receive convert signals into heat, thereby initiating of lysis proteins under control a heat-sensitive promoter. then lyse, releasing its anti-CD47 nanobody cargo, that is pre-expressed within bacteria. robust immunogenicity lysate cooperates activate both innate adaptive immune responses, generating antitumor effects against not only but also distal mice. magnetically constant field-controlled motion enhanced targeting increased therapeutic efficacy. Thus, behavior can manipulated vivo field, achieving tumor-specific CD47 blockage precision immunotherapy.

Language: Английский

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Engineered Living Materials for Advanced Diseases Therapy

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: July 12, 2023

Abstract Natural living materials serving as biotherapeutics exhibit great potential for treating various diseases owing to their immunoactivity, tissue targeting, and other biological activities. In this review, the recent developments in engineered materials, including mammalian cells, bacteria, viruses, fungi, microalgae, plants, active derivatives that are used summarized. Further, future perspectives challenges of such material‐based discussed provide considerations advances biomedical applications.

Language: Английский

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Sequential Targeting Hybrid Nanovesicles Composed of Chimeric Antigen Receptor T-Cell-Derived Exosomes and Liposomes for Enhanced Cancer Immunochemotherapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(17), P. 16770 - 16786

Published: Aug. 25, 2023

Paclitaxel (PTX)-based chemotherapy remains the main approach to treating lung cancer but systemic toxicity limits its use. As chimeric antigen receptor-T (CAR-T) cell-derived exosomes contain tumor-targeted CARs and cytotoxic granules (granzyme B perforin), they are considered potential delivery vehicles for PTX. However, low drug-loading capacity hepatotropic properties of obstacles their application extrahepatic cancer. Here, a hybrid nanovesicle named Lip-CExo@PTX was designed immunochemotherapy by fusing derived from bispecific CAR-T cells targeting both mesothelin (MSLN) programmed death ligand-1 (PD-L1) with lung-targeted liposomes. Due lung-targeting ability liposomes, over 95% intravenously administered accumulated in tissue. In addition, help anti-MSLN single-chain variable fragment (scFv), PTX inside were further delivered into MSLN-positive tumors. Notably, anti-PD-L1 scFv on blocked PD-L1 tumors avoid T cell exhaustion promoted PTX-induced immunogenic death. Furthermore, prolonged survival time tumor-bearing mice CT-26 metastatic model. Therefore, may deliver tumor through sequential targeted enhance antitumor effects, providing promising strategy

Language: Английский

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Advances in Engineered Macrophages: A New Frontier in Cancer Immunotherapy

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 1, 2024

Abstract Macrophages, as pivotal cells within the tumour microenvironment, significantly influence impact of and reactions to treatments for solid tumours. The rapid evolution bioengineering technology has revealed vast potential engineered macrophages in immunotherapy, disease diagnosis, tissue engineering. Given this landscape, goal harnessing innovating a novel strategy immunotherapy cannot be overstated. diverse strategies realm cancer encompassing macrophage drug delivery systems, chimeric antigen receptor therapy, synergistic treatment approaches involving bacterial outer membrane vesicles macrophages, are meticulously examined review. These methodologies designed enhance therapeutic efficacy against tumours, particularly those that drug-resistant metastatic. Collectively, these immunotherapies poised supplement refine current paradigms, thus heralding new frontier fight malignant

Language: Английский

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Engineered bacterial outer membrane vesicles: a versatile bacteria-based weapon against gastrointestinal tumors

Theranostics, Journal Year: 2024, Volume and Issue: 14(2), P. 761 - 787

Published: Jan. 1, 2024

Outer membrane vesicles (OMVs) are nanoscale lipid bilayer structures released by gram-negative bacteria.They share composition and properties with their originating cells, making them adept at traversing cellular barriers.These OMVs have demonstrated exceptional stability, immunogenicity, safety, penetration, tumor-targeting properties, which been leveraged in developing vaccines drug delivery systems.Recent research efforts focused on engineering to increase production yield, reduce cytotoxicity, improve the safety efficacy of treatment.Notably, gastrointestinal (GI) tumors proven resistant several traditional oncological treatment strategies, including chemotherapy, radiotherapy, targeted therapy.Although immune checkpoint inhibitors some patients, usage as monotherapy remains limited tumor heterogeneity individual variability.The immunogenic modifiable nature makes an ideal design platform for individualized GI tumors.OMV-based therapy enables combination optimization anti-tumor effects.This review comprehensively summarizes recent advances OMV discusses challenges clinical translation emerging OMV-based therapies.

Language: Английский

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Opportunities and challenges of bacterial extracellular vesicles in regenerative medicine

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 3, 2025

Language: Английский

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Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances biotechnology have revealed potential bacteria their derivatives as drug delivery systems for tumor therapy by leveraging biological properties. Engineered bacteria, Escherichia coli, Salmonella, Listeria monocytogenes, along with derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), spores (BSPs)─can be loaded a variety antitumor agents, enabling precise targeting sustained release within microenvironment (TME). These possess intrinsic properties that stimulate immune system, enhancing both innate adaptive responses to further amplify therapeutic effects. The ability naturally accumulate hypoxic regions versatility genetic modifications allow tailored strategies synergistically enhance effectiveness chemotherapy, immunotherapy, targeted therapies. This review comprehensively examines fundamental principles therapy, focusing on employed engineering, loading, use therapy. It also discusses challenges faced optimizing systems, such safety concerns, unintended responses, scalability clinical applications. By exploring these aspects, this provides theoretical framework improving bacterial-based contributing more effective personalized treatments.

Language: Английский

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Transforming Intratumor Bacteria into Immunopotentiators to Reverse Cold Tumors for Enhanced Immuno-chemodynamic Therapy of Triple-Negative Breast Cancer

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(48), P. 26296 - 26307

Published: Nov. 21, 2023

Immunotherapy of triple-negative breast cancer (TNBC) has an unsatisfactory therapeutic outcome due to immunologically "cold" microenvironment. Fusobacterium nucleatum (F. nucleatum) was found be colonized in tumors and responsible for the immunosuppressive tumor microenvironment metastasis. Herein, we constructed a bacteria-derived outer membrane vesicle (OMV)-coated nanoplatform that precisely targeted tissues dual killing F. cells, thus transforming intratumor bacteria into immunopotentiators immunotherapy TNBC. The as-prepared nanoparticles efficiently induced immunogenic cell death through Fenton-like reaction, resulting enhanced immunogenicity. Meanwhile, intratumoral killed by metronidazole, release pathogen-associated molecular patterns (PAMPs). PAMPs cooperated with OMVs further facilitated maturation dendritic cells subsequent T-cell infiltration. As result, "kill two birds one stone" strategy warmed up cold environment, maximized antitumor immune response, achieved efficient therapy TNBC as well metastasis prevention. Overall, this based on microecology distinction normal tissue microbiome-induced reversal provides new insight precise

Language: Английский

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