A Targeted Nanotoxin Inhibits Colorectal Cancer Growth Through Local Tumor Pyroptosis and Eosinophil Infiltration and Degranulation DOI Creative Commons
Luis Miguel Carrasco-Díaz, Alberto Gallardo, Eric Voltà‐Durán

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 2445 - 2460

Published: Feb. 1, 2025

Colorectal cancer (CRC) has traditionally been treated with genotoxic chemotherapy to activate pro-apoptotic proteins induce anticancer effects. However, cells develop resistance apoptosis, which leads recurrence and poor prognosis. Moreover, this kind of therapy shown be highly toxic healthy tissues and, therefore, patients. To overcome issue, we developed a self-assembly tumor-targeted nanoparticle, T22-DITOX-H6, that incorporates the T22 peptide (a CXCR4 ligand) selectively target overexpressing CXCR4, fused catalytic domain diphtheria toxin, exhibits potent cytotoxic effect on these CXCR4+ effects CXCR4-overexpressing through activation pyroptosis, an immunogenic type cell death. CXCR4-expressing tumor (CT26-CXCR4+) were implanted subcutaneously into immunocompetent mice study T22-DITOX-H6 treatment growth, death innate immune recruitment tumor. Here, demonstrated nanoparticle activated differs from leading in cells, without affecting viability CXCR4-lacking cells. In addition, administered tumor-bearing induced local antitumor due selective pyroptosis targeted Biochemical analysis plasma histological non-tumor revealed no differences between groups. Remarkably, stimulates eosinophil infiltration microenvironment, recently reported have anti-tumorigenic function. These results highlight dual role CXCR4-targeted eliminating boosting self-immune response compromising organs.

Language: Английский

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

12
Stimuli-Responsive Polymers at the Interface with Biology DOI
Nathan R. B. Boase, Elizabeth R. Gillies, Rubayn Goh

et al.

Biomacromolecules, Journal Year: 2024, Volume and Issue: 25(9), P. 5417 - 5436

Published: Aug. 28, 2024

There has been growing interest in polymeric systems that break down or undergo property changes response to stimuli. Such polymers can play important roles biological systems, where they be used control the release of therapeutics, modulate imaging signals, actuate movement, direct growth cells. In this Perspective, after discussing most stimuli relevant applications, we will present a selection recent exciting developments. The importance stimuli-responsive polysaccharides discussed, followed by variety for delivery small molecule drugs and nucleic acids. Switchable emerging area therapeutic measurement theranostics described. Then, diverse functions achieved using hydrogels cross-linked covalently, as well various dynamic approaches presented. Finally, discuss some challenges future perspectives field.

Language: Английский

Citations

12
Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade DOI
Minjie Fu, Jiaxu Zhao, Licheng Zhang

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1882 - 1897.e7

Published: Oct. 17, 2024

Language: Английский

Citations

10
Inflammation and Immune Escape in Ovarian Cancer: Pathways and Therapeutic Opportunities DOI Creative Commons
Chunyan Liu, Qinan Yin,

Zhaoying Wu

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 895 - 909

Published: Jan. 1, 2025

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to its late-stage diagnosis and high recurrence rates. Chronic inflammation is a critical driver OC progression, contributing immune evasion, tumor growth, metastasis. Inflammatory cytokines, including IL-6, TNF-α, IL-8, as well key signaling pathways such nuclear factor kappa B (NF-kB) signal transducer activator transcription 3 (STAT3), are upregulated in OC, promoting tumor-promoting environment. The microenvironment (TME) characterized by cells like tumor-associated macrophages (TAMs) regulatory T (Tregs), which suppress anti-tumor responses, facilitating evasion. Furthermore, utilize checkpoint pathways, PD-1/PD-L1, inhibit cytotoxic cell activity. Targeting these inflammatory evasion mechanisms offers promising therapeutic strategies. COX-2 inhibitors, Janus kinase/signal (JAK/STAT) pathway blockers, NF-kB inhibitors have shown potential preclinical studies, while targeting PD-1/PD-L1 CTLA-4 been explored with mixed results OC. Additionally, emerging research on microbiome inflammation-related biomarkers, microRNAs (miRNAs) exosomes, points new opportunities for early detection precision medicine. Future approaches treatment must focus personalized strategies that target TME, integrating anti-inflammatory therapies immunotherapy enhance patient outcomes. Continued into interplay between essential developing effective, long-lasting treatments.

Language: Английский

Citations

1
Drug Delivery Systems Based on Metal–Organic Frameworks for Tumor Immunotherapy DOI Creative Commons
Ning Yang,

Zongyan He,

Tianqun Lang

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 225 - 225

Published: Feb. 10, 2025

Metal–organic frameworks (MOFs) are a class of inorganic-organic hybrid nanoparticles formed by the coordination metal ions/clusters and organic ligands. Due to their high porosities, large surface areas, adjustable structures, responsiveness light/sound, etc., MOFs have shown great clinical potential in field tumor therapy. Tumor immunotherapy exerts antitumor effects through reshaping immune microenvironment, showing significant preclinical advantages. Based on mechanisms immunity activation, agents can be divided into chemotherapeutic agents, immunomodulators, enzymes, vaccines oligonucleotide drugs, etc. Herein, we review MOFs-based drug delivery systems for immunotherapy. The classification MOFs, followed activation mechanisms, first introduced. Drug based with different also summarized, especially synergetic triggered loadings. Furthermore, merits drawbacks strategies promote applications discussed.

Language: Английский

Citations

1
Challenges and Material Innovations in Drug Delivery to Central Nervous System Tumors DOI
Zhenyu Gong,

Dairan Zhou,

Dejun Wu

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123180 - 123180

Published: Feb. 13, 2025

Language: Английский

Citations

1
Strategies to Overcome Antigen Heterogeneity in CAR-T Cell Therapy DOI Creative Commons
Bohan Zhang, Jiawen Wu,

Hua Jiang

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 320 - 320

Published: Feb. 20, 2025

Chimeric antigen receptor (CAR) gene-modified T-cell therapy has achieved significant success in the treatment of hematological malignancies. However, this not yet made breakthroughs solid tumors and still faces issues resistance relapse cancers. A major reason for these problems is antigenic heterogeneity tumor tissues. This review outlines encountered CAR-T cell corresponding strategies to address it. These include using combination increase abundance target antigens, optimizing structure CARs enhance sensitivity low-density developing multi-targeted cells, reprogramming TME activate endogenous immunity. approaches offer new directions overcoming therapy.

Language: Английский

Citations

1
Genome‐wide profiling of N6‐methyladenosine‐modified pseudogene‐derived long noncoding RNAs reveals the tumour‐promoting and innate immune‐restraining function of RPS15AP12 in ovarian cancer DOI Creative Commons
Jie Xu, Yifei Ren, Jiayi Lu

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Abstract Background Pseudogene‐derived lncRNAs are widely dysregulated in cancer. Technological advancements have facilitated the functional characterization of increasing pseudogenes cancer progression. However, association between and RNA N6‐methyladenosine (m 6 A) modification cancer, as well underlying mechanisms, remains largely unexplored. Methods We analyzed expression 12 146 comprehensively examined m A RNAs derived from them their paralogs. Through integrative analysis multi‐omics data, we explored associations pseudogene dysregulation A, identifying critical involved HGSOC Tumour promotion role RPS15AP12 its cognate parent gene was characterized by cell proliferation, transwell assays, scratch assays ovarian cells xenograft nude mice. decay were used to reveal participation decreasement lncRNA stability. Luciferase reporter performed verify that enhances RPS15A competitively binding miR‐96‐3p. Western blot phosphorylation investigate impairment towards sensors MAVS (RIG‐I MDA5), downstream p‐TBK1 p‐IRF3. Finally, ELISA explore regulatory IFN‐β expression. Results M is distributed across over a thousand pseudogenes, hypomethylation leads upregulation HGSOC. identified processed pseudogene, RPS15AP12, upregulated FTO‐mediated demethylation. growth ability metastatic capabilities (OC) via functioning competitive endogenous (ceRNA) for host gene, RPS15A, through sequestration Importantly, deletion diminishes leading anti‐tumour immune responses activating RIG‐I MDA5 p‐IRF3 levels. Conclusion Our findings expand understanding A‐modulated tumour innate immunity OC. Key Points Genome‐wide profiling reveals redistribution m6A on pseudogene‐derived redistribution‐relevant representative up‐regulated demethylation acts miRNA sponge promote RPS15AP12/RPS15A axis inhibits MDA5) levels

Language: Английский

Citations

1
Friend or Foe: Exploring the Relationship between the Gut Microbiota and the Pathogenesis and Treatment of Digestive Cancers DOI Creative Commons
Monica Profir,

Oana Roşu,

Sanda Maria Creţoiu

et al.

Microorganisms, Journal Year: 2024, Volume and Issue: 12(5), P. 955 - 955

Published: May 8, 2024

Digestive cancers are among the leading causes of cancer death in world. However, mechanisms development and progression not fully understood. Accumulating evidence recent years pointing to bidirectional interactions between gut dysbiosis a specific type gastrointestinal is shedding light on importance this “unseen organ”—the microbiota. This review focuses local role microbiota imbalance different digestive tract organs annexes related carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or dietary changes, plays an important future therapies various cancers.

Language: Английский

Citations

7
Dual‐Engineered Macrophage‐Microbe Encapsulation for Metastasis Immunotherapy DOI
Leyang Wu,

Liyuan Qiao,

Shu‐Hui Zhang

et al.

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

Published: July 18, 2024

Abstract Lung metastases are the leading cause of death among cancer patients. The challenges inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual‐engineered macrophage‐microbe encapsulation (Du‐EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria. These macrophages, termed R‐GEM cells, designed to express RGD peptides on extracellular membranes, enhancing their tumor cell binding intratumor enrichment. cells cocultured with attenuated Salmonella typhimurium VNP20009, producing (R‐GEM/VNP cells). intracellular bacteria maintain bioactivity for more than 24 h, released from R‐GEM/VNP within continue exert bacteria‐mediated effects. This further supported macrophage‐based chemotaxis camouflage, which enhance intratumoral enrichment biocompatibility Additionally, loaded IFNγ‐secreting strains (VNP‐IFNγ) form R‐GEM/VNP‐IFNγ cells. Treatment these effectively halts lung metastatic progression in three mouse models (breast cancer, melanoma, colorectal cancer). vigorously activate suppressing tumor‐promoting M2‐type MDSCs, Tregs, tumor‐antagonizing M1‐type mature DCs, Teffs. Du‐EMME offers promising strategy targeted enhanced immunity treating metastases.

Language: Английский

Citations

7