Targeting Metabolic Adaptation of Colorectal Cancer with Vanadium‐Doped Nanosystem to Enhance Chemotherapy and Immunotherapy DOI Creative Commons

Qian Cheng,

Yu‐Zhe Chen,

Danyi Zou

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

The anti-tumor efficacy of current pharmacotherapy is severely hampered due to the adaptive evolution tumors, urgently needing effective therapeutic strategies capable breaking such adaptability. Metabolic reprogramming, as an survival mechanism, closely related therapy resistance tumors. Colorectal cancer (CRC) cells exhibit a high energy dependency that sustained by metabolic conversion between glucose and glutamine, helping tumor withstand nutrient-deficient microenvironments various treatments. We discover transition metal vanadium (V) effectively inhibits metabolism in CRC synergizes with glutaminase inhibitors (BPTES) disrupt CRC's dependency. Thus, dual suppression nanosystem (VSi-BP@HA) engineered loading BPTES into V-doped hollow mesoporous silica nanoparticles. This dampens metabolism, eradicating 33% tumors mice. Strikingly, cell biological preclinical model datasets provide compelling evidence showing VSi-BP@HA not only reverses chemo-resistance but also drastically potentiates anti-PD1 immunotherapy. Therefore, this provides promising approach suppress CRC, potential adjunct tool for enhancing chemotherapy

Language: Английский

Mitochondria‐Targeted Nanoadjuvants Induced Multi‐Functional Immune‐Microenvironment Remodeling to Sensitize Tumor Radio‐Immunotherapy DOI Creative Commons
Zaigang Zhou, Cheng Li, Chao Li

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(26)

Published: May 5, 2024

Abstract It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair trigger T cell exclusion limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective simultaneously, effectively, easily. In this study, it inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) serve multi‐immune pathway regulation strategy through PD‐L1, collagen, TGF‐β co‐depression. Then, IR‐LND prepared combining mitochondria‐targeted molecule IR‐68 with LND, which then loaded liposomes (Lip) create IR‐LND@Lip nanoadjuvants. By doing this, more effectively sensitizes generating cold tumors into hot ones activation co‐inhibition. conclusion, combined treatment ultimately almost completely suppressed bladder breast

Language: Английский

Citations

17
Nanomaterials in cancer immunotherapy: targeting cancer-associated fibroblasts DOI Creative Commons

Zhongsong Zhang,

Long Chen

Cancer Nanotechnology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 17, 2025

Emphasizing the significance of cancer-associated fibroblasts (CAFs), non-malignant yet pivotal players within tumor microenvironment (TME), this review illuminates role inflammatory subtype (iCAF) as catalysts in cancer proliferation, metastasis, and therapeutic resistance. Given their paramount importance, targeting CAFs emerges a robust strategy evolving landscape immunotherapy. Nanomaterials, distinguished by unique features malleability, hold considerable promise biomedicine, especially precision-oriented domain therapy. Their aptitude for modulating immune responses, amplifying drug efficacy through precise delivery, discerningly focusing on cells TME situates nanomaterials formidable tools to transcend boundaries set conventional treatments. This scrutinizes convoluted interplay among CAFs, cells, TME. It further showcases widely utilized management. We underscore potential nanoscale delivery systems directed at underscoring transformative power revolutionizing therapies, enhancing precision, culminating improved patient outcomes.

Language: Английский

Citations

2
A novel silkworm excrement-derived nanomedicine integrating ferroptosis and photodynamic therapy, well-suitable for PD-L1-mediated immune checkpoint blockade DOI
Yujun Bao, Guanghao Li, Mingyang Liu

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 505, P. 159676 - 159676

Published: Jan. 17, 2025

Language: Английский

Citations

2
Targeting TRAP1-Dependent Metabolic Reprogramming to Overcome Doxorubicin Resistance in Quiescent Breast Cancer DOI Creative Commons
Muhammad Zubair Saleem, Ruyi Huang, Yingying Huang

et al.

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 81, P. 101226 - 101226

Published: March 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.

Language: Английский

Citations

1
A mitochondria-interfering nanocomplex cooperates with photodynamic therapy to boost antitumor immunity DOI
Zhijie Zhang,

Qingfu Zhao,

Qingqing Xu

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 317, P. 123094 - 123094

Published: Jan. 7, 2025

Language: Английский

Citations

0
Computer‐Aided Design of Self‐Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual‐Modulation Strategy DOI Open Access
Xiaoting Shan, Ying Cai,

Binyu Zhu

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

0
Enzymatically responsive nanocarriers targeting PD-1 and TGF-β pathways reverse immunotherapeutic resistance and elicit robust therapeutic efficacy DOI Creative Commons
Ying‐Tzu Yen, Zhifan Zhang, Anni Chen

et al.

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

Published: Feb. 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.

Language: Английский

Citations

0
Multifunctional nanoparticle-mediated targeting of metabolic reprogramming and DNA damage response pathways to treat drug-resistant triple-negative breast cancer DOI
Sifeng Zhu, Chao Sun,

Zimin Cai

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 381, P. 113601 - 113601

Published: March 5, 2025

Language: Английский

Citations

0
Biogenic nanoparticles: Understanding their potential role in cancer theranostics DOI Creative Commons
Durdana Yasin,

Neha Sami,

Bushra Afzal

et al.

Next Nanotechnology, Journal Year: 2025, Volume and Issue: 8, P. 100149 - 100149

Published: Jan. 1, 2025

Language: Английский

Citations

0
Halofuginone Disrupted Collagen Deposition via mTOR‐eIF2α‐ATF4 Axis to Enhance Chemosensitivity in Ovarian Cancer DOI Creative Commons
Wenxin Li, Yenan Wu, Yanan Zhang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

The interplay between cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) mediates progress, metastasis, therapy resistance. However, strategy of targeting ECM remodeling to enhance chemosensitivity in ovarian cancer remains elusive. Here, a 22-gene matrisome signature predicts chemotherapy response survival cancer. dense, collagen-rich secreted by CAFs harbors more M2 tumor-associated macrophages (TAMs) than the looser based on single cell RNA-seq (scRNA-seq) cancer, suggesting promising approach collagen remodel ECM. An integrated analysis identifies type I alpha 1 chain (COL1A1) as major component that contributes chemoresistance poor prognosis, highlighting its potential therapeutic target. Halofuginone (HF), clinically active derivative febrifugine, is identified COL1A1-targeting natural compound screening Encyclopedia Traditional Chinese Medicine (ETCM). Mechanistically, HF inhibits COL1A1 production via mTOR-eIF2α-ATF4 axis CAFs. Notably, disrupts deposition promotes CD8+ T infiltration, partially M2-M1 macrophage polarization chemosensitivity. Overall, findings suggest combined with effective treatment for

Language: Английский

Citations

0