Mitochondria Energy Metabolism Depression as Novel Adjuvant to Sensitize Radiotherapy and Inhibit Radiation Induced‐Pulmonary Fibrosis

Advanced Science, Год журнала: 2024, Номер 11(26)

Опубликована: Май 7, 2024

Abstract Currently, the typical combination therapy of programmed death ligand‐1 (PD‐L1) antibodies with radiotherapy (RT) still exhibits impaired immunogenic antitumor response in clinical due to lessened DNA damage and acquired immune tolerance via upregulation some other checkpoint inhibitors. Apart from this, such may raise occurrence rate radiation‐induced lung fibrosis (RIPF) enhanced systemic inflammation, leading ultimate cancer patients (average survival time about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD‐L1 transforming growth factor‐β (TGF‐β) dual‐downregulation method. Following IR‐TAM prepared by conjugating mitochondria‐targeted heptamethine cyanine dye IR‐68 oxidative phosphorylation (OXPHOS) inhibitor Tamoxifen (TAM), which then self‐assembled albumin (Alb) form IR‐TAM@Alb nanoparticles. By doing tumor‐targeting nanoparticle effectively reversed tumor hypoxia depressed TGF‐β expression sensitize RT. Meanwhile, capacity targeting RIPF function TAM depressing TGF‐β, also ameliorated development induced

Язык: Английский

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Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(9), С. 4087 - 4101

Опубликована: Июнь 3, 2024

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to impaired PTX@Alb accumulation in tumors partly mediated by dense collagen distribution. Meanwhile, acquired immune resistance always occurs enhanced programmed cell death-ligand 1 (PD-L1) expression after treatment, which then leads tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be as novel effective PD-L1 and TGF-

Язык: Английский

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A novel silkworm excrement-derived nanomedicine integrating ferroptosis and photodynamic therapy, well-suitable for PD-L1-mediated immune checkpoint blockade

Chemical Engineering Journal, Год журнала: 2025, Номер 505, С. 159676 - 159676

Опубликована: Янв. 17, 2025

Язык: Английский

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Targeting TRAP1-Dependent Metabolic Reprogramming to Overcome Doxorubicin Resistance in Quiescent Breast Cancer

Drug Resistance Updates, Год журнала: 2025, Номер 81, С. 101226 - 101226

Опубликована: Март 3, 2025

TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1. Breast were induced quiescence hypoxia low glucose. The relationship cell metabolism with was investigated Western blotting, ECAR, OCR, mitochondrial complex activity, proteomic analysis. targets C210 their functions analyzed SPR immunoprecipitation. antitumor effect vivo mouse tumor model. In glucose deprivation, exhibited elevated an OXPHOS-enhanced phenotype. These highly resistant DOX but more sensitive C210. disrupted TRAP1's interaction OXPHOS-associated client proteins, prompting proteasome-dependent degradation these thereby reducing ATP production resulting selective elimination the inducing apoptosis which could be reversed exogenous ATP. Moreover, targeted glycolytic, amino acid, β-oxidation-associated proteome. demonstrated promising anticancer efficacy particularly related OXPHOS inhibition. eliminates DOX-resistant TRAP1-dependent bioenergetics.

Язык: Английский

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A mitochondria-interfering nanocomplex cooperates with photodynamic therapy to boost antitumor immunity

Biomaterials, Год журнала: 2025, Номер 317, С. 123094 - 123094

Опубликована: Янв. 7, 2025

Язык: Английский

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Computer‐Aided Design of Self‐Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual‐Modulation Strategy

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 19, 2025

Abstract The rational design of self‐assembled compounds is crucial for the highly efficient development carrier‐free nanomedicines. Herein, based on computer‐aided strategies, important physicochemical properties are identified to guide compounds. Then, pharmacophore hybridization strategy used self‐assemble nanoparticles by preparing new chemical structures combining groups different bioactive Hydroxychloroquine grafted with lipophilic vitamin E succinate and then co‐assembled bortezomib fabricate nanoparticle. nanoparticle can reduce M2‐type tumor‐associated macrophages (TAMs) through lysosomal alkalization induce immunogenic cell death (ICD) nuclear factor‐κB (NF‐κB) inhibition in tumor cells. In mouse models, decreased levels TAMs, regulatory T cells, transforming growth factor‐β (TGF‐β), increase proportion cytotoxicity lymphocytes. Additionally, secretion Interleukin‐6 (IL‐6) inhibiting NF‐κB enhance programmed ligand‐1 (PD‐L1) checkpoint blockade therapy. hybridization‐derived provides a dual‐modulation reprogram microenvironment, which will efficiently chemoimmunotherapy against triple‐negative breast cancer.

Язык: Английский

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Enzymatically responsive nanocarriers targeting PD-1 and TGF-β pathways reverse immunotherapeutic resistance and elicit robust therapeutic efficacy

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 19, 2025

Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment, yet resistance remains a challenge. Co-inhibition of PD-1/PD-L1 and TGF-β shows promise but faces limited efficacy systemic toxicity. We developed gelatinase-responsive nanoparticles (GPNPs) delivering anti-PD-1 antibody (αPD-1) receptor I inhibitor galunisertib (Gal). GPNPs effectively inhibit tumor progression without observed side effects. profiling by cytometry assay reveals robust recruitment both activated exhausted tumor-infiltrating lymphocytes (TILs) macrophages. Transcriptomic analysis indicates extracellular matrix modulation, supported reduced collagen deposition αSMA expression. Fate mapping demonstrates attenuation Pdgfrα+ fibroblast transition to myofibroblasts, potentially reversing "immune-exclusive" status. This study validates as promising immunotherapy platform, offering mechanistic insights for clinical translation therapeutic enhancement.

Язык: Английский

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The critical role of immune response in lung cancer and its treatment progress

New discovery., Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Фев. 28, 2025

Lung cancer, one of the most malignant tumors globally, continues to pose a significant threat human health due its high morbidity and mortality. While traditional treatments have made strides in controlling tumor growth, they often come with severe side effects. With advancements medical technology, immunotherapy has emerged as promising approach, yet there remains lack comprehensive research summarizing these methods. This paper aims review current progress for lung cancer. Conducted methods involved searching key terms such immune response cancer PubMed database, focusing on related classification, mechanisms, therapeutic strategies over past decade. The results highlight background, types, epidemiology, treatment status, anti-tumor immunity, checkpoint inhibitors, various so offer critical insights clinicians researchers lay out valuable references promote effective management

Язык: Английский

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Highly Efficient Bifunctional Peptides for Tumor Immunotherapy by Simultaneously Activating T Cells and Blocking PD-L1 Immune Checkpoint

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have shown great success in tumor immunotherapy. However, the response rate of immune blockade (ICB) therapy alone is far from satisfactory due to insufficient and exhausted tumor-infiltrating T cells. Meanwhile, antibody-based drugs some drawbacks such as high cost complicated preparation, which require further development nonantibody more rational strategies for improving effectiveness treatment. Here, a highly efficient bifunctional peptide (Bi-pep) was constructed treatment simultaneously activating cells blocking PD-L1 checkpoint. This not only can block immunosuppressive pathway but also directly efficiently promote activation proliferation cells, thereby showing significant effect on promoting cell killing The Bi-pep-induced antitumor verified both subcutaneous orthotopic models, significantly inhibit growth thus prolong survival tumor-bearing mice, holding potential biomedical applications.

Язык: Английский

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Biogenic nanoparticles: Understanding their potential role in cancer theranostics

Next Nanotechnology, Год журнала: 2025, Номер 8, С. 100149 - 100149

Опубликована: Янв. 1, 2025

Язык: Английский

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