Configuration‐Mediated Efficient Non‐Radiative Transition for R848‐Assisted Photothermal Immunotherapy to Inhibit Tumor Growth and Metastasis by An In Situ Tumor Vaccine Strategy DOI
Jianan Dai, Laiping Fang, Xuan Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Cancer metastasis remains a critical factor contributing to the current limitations in cancer treatment. Photothermal immunotherapy has emerged as safe and potent therapeutic approach, demonstrating capability suppress tumor growth metastasis. While researchers have extensively investigated various structural modifications enhance photothermal conversion performance, influence of molecular configuration received comparatively limited attention. In this study, we synthesized two isomers, CZTBT LVTBT, which possessed distinct configurations. characterized by flatter configuration, exhibited an extended absorption wavelength higher molar extinction coefficient. Its excited state facilitated stronger rotation for non-radiative transitions, leading high efficiency (PCE) 36.3 %. When combined with R848, LVTBT@R848 nanoparticles (NPs)-mediated functioned situ vaccine, promoting maturation dendritic cells (DCs), T cell infiltration, differentiation natural killer (NK) memory cells, thereby activating strong immune response. Consequently, it significantly inhibited both primary distant tumors, while also limiting lung summary, study proposed configuration-mediated transition strategy efficient immunotherapy, advancing frontiers organic agents (OPTAs) design synthesis.

Language: Английский

Exogenous RNA surveillance by proton-sensing TRIM25 DOI
Myeonghwan Kim, Youngjoon Pyo, Seong‐In Hyun

et al.

Science, Journal Year: 2025, Volume and Issue: 388(6742)

Published: April 4, 2025

Exogenous messenger RNAs (mRNAs) require cellular machinery for delivery and translation but also encounter inhibitory factors. To investigate their regulation, we performed genome-wide CRISPR screens with in vitro–transcribed mRNAs lipid nanoparticles (LNPs). Heparan sulfate proteoglycans (HSPGs) vacuolar adenosine triphosphatase (V-ATPase) were identified as mediators of LNP uptake endosomal escape, respectively. TRIM25—an RNA binding E3 ubiquitin ligase—emerged a key suppressor inducing turnover both linear circular mRNAs. The endoribonucleases N4BP1 KHNYN, along the antiviral protein ZAP, act redundantly TRIM25-dependent surveillance. TRIM25 specifically targets delivered by endosomes, its affinity increases at acidic pH, suggesting activation protons released from ruptured endosomes. N 1 -methylpseudouridine modification reduces TRIM25’s binding, helping evade suppressive effect. This study comprehensively maps pathways regulating LNP-mRNAs, offering insights into immunity therapeutics.

Language: Английский

Citations

0
An evolutionary perspective to innate antiviral immunity in animals DOI Creative Commons
João T. Marques, Carine Meignin, Jean‐Luc Imler

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114678 - 114678

Published: Aug. 27, 2024

Viruses pose a significant threat to cellular organisms.Innate antiviral immunity encompasses both RNA-and protein-based mechanisms designed sense and respond infections, fundamental aspect present in all living organisms.A potent RNA-based mechanism is RNA interference, where small RNA-programmed nucleases target viral RNAs.Protein-based often rely on the induction of transcriptional responses triggered by recognition infections through innate immune receptors.These involve upregulation genes aimed at countering infections.In this review, we delve into recent advances understanding diversification animals.An evolutionary perspective gains losses diverse animals coupled mechanistic studies model organisms such as fruit fly Drosophila melanogaster essential provide deep that can be translated new strategies treatment diseases.

Language: Английский

Citations

3
The path ahead for understanding Toll-like receptors–driven systemic autoimmunity DOI
Jessica A. Hamerman, Gregory M. Barton

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 91, P. 102482 - 102482

Published: Sept. 30, 2024

Language: Английский

Citations

3
2’-O-Methyl-guanosine 3-base RNA fragments mediate essential natural TLR7/8 antagonism DOI Creative Commons
Arwaf Alharbi, Sunil Sapkota,

Zhikuan Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 25, 2024

Abstract Recognition of RNA fragments by Toll-like receptors (TLR) 7 and 8 is a key contributor to the initiation protective innate immune response against pathogens. A long-standing enigma how degradation products host RNAs, generated daily phagocytic clearance billions apoptotic cells, fail activate TLR7 TLR8 signalling 1 . Here, we report that select 2’-O-methyl (2’-Ome) guanosine as short 3 bases, including those derived from host-RNAs, are potent antagonists reduce sensing in vivo Mechanistically, antagonistic directed towards distinct binding site on these proteins 5’-end 2’-Ome guanosine. Our results indicate host-RNAs evade detection TLR7/8 due pool abundant ribosomal 2’-Ome-modified naturally antagonize avoid auto-immunity. Crucially, rare mutations located at this decrease inhibitory activity lead auto-immunity patients. findings also establish chemically synthesised 3-base oligonucleotides can harness anti-inflammatory natural checkpoint for therapeutic targeting TLR7-driven diseases. One Sentence Summary Short 2’-O-Methyl

Language: Английский

Citations

2
Fraternal twins at work: Structures of PLD3/4 reveal mechanism for lysosomal nucleic acid breakdown DOI
Oliver Daumke, Markus Daμμe

Structure, Journal Year: 2024, Volume and Issue: 32(6), P. 645 - 647

Published: June 1, 2024

Language: Английский

Citations

0
miR-574-5p in epigenetic regulation and Toll-like receptor signaling DOI Creative Commons

James Y. Yang

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 26, 2024

miR-574-5p is an unusual microRNA (miRNA) that often upregulated or downregulated following exposure to irradiation toxic chemicals; bacterial, parasitic viral infection; and a variety of other disease conditions. Canonically, epigenetically regulates the expression many messenger RNAs (mRNAs) through miRNA-mediated posttranscriptional regulation, thereby affecting cellular physiology pathophysiology contributing pathogenesis progression diseases. However, recent studies have established in addition serving as fine-tuning repressor gene expression, also stimulates endogenous ligand for Toll-like receptor-8/7 (TLR8/7). Indeed, binding TLR8/7 triggers TLR signaling pathway, leading induction interferons, inflammatory cytokines autoimmune signaling. These findings suggest not only important epigenetic regulator but immune responses. Abnormal miR-574-5p-TLR8/7 has been shown be tightly associated with inflammation-related cancers number disorders. can serve potential biomarker Most importantly, promising therapeutic target treatment prevention human disorders, especially infectious diseases,

Language: Английский

Citations

0
Configuration‐Mediated Efficient Non‐Radiative Transition for R848‐Assisted Photothermal Immunotherapy to Inhibit Tumor Growth and Metastasis by An In Situ Tumor Vaccine Strategy DOI
Jianan Dai, Laiping Fang, Xuan Wang

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Abstract Cancer metastasis remains a critical factor contributing to the current limitations in cancer treatment. Photothermal immunotherapy has emerged as safe and potent therapeutic approach, demonstrating capability suppress tumor growth metastasis. While researchers have extensively investigated various structural modifications enhance photothermal conversion performance, influence of molecular configuration received comparatively limited attention. In this study, we synthesized two isomers, CZTBT LVTBT, which possessed distinct configurations. characterized by flatter configuration, exhibited an extended absorption wavelength higher molar extinction coefficient. Its excited state facilitated stronger rotation for non‐radiative transitions, leading high efficiency (PCE) 36.3 %. When combined with R848, LVTBT@R848 nanoparticles (NPs)‐mediated functioned situ vaccine, promoting maturation dendritic cells (DCs), T cell infiltration, differentiation natural killer (NK) memory cells, thereby activating strong immune response. Consequently, it significantly inhibited both primary distant tumors, while also limiting lung summary, study proposed configuration‐mediated transition strategy efficient immunotherapy, advancing frontiers organic agents (OPTAs) design synthesis.

Language: Английский

Citations

0
Configuration‐Mediated Efficient Non‐Radiative Transition for R848‐Assisted Photothermal Immunotherapy to Inhibit Tumor Growth and Metastasis by An In Situ Tumor Vaccine Strategy DOI
Jianan Dai, Laiping Fang, Xuan Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Cancer metastasis remains a critical factor contributing to the current limitations in cancer treatment. Photothermal immunotherapy has emerged as safe and potent therapeutic approach, demonstrating capability suppress tumor growth metastasis. While researchers have extensively investigated various structural modifications enhance photothermal conversion performance, influence of molecular configuration received comparatively limited attention. In this study, we synthesized two isomers, CZTBT LVTBT, which possessed distinct configurations. characterized by flatter configuration, exhibited an extended absorption wavelength higher molar extinction coefficient. Its excited state facilitated stronger rotation for non-radiative transitions, leading high efficiency (PCE) 36.3 %. When combined with R848, LVTBT@R848 nanoparticles (NPs)-mediated functioned situ vaccine, promoting maturation dendritic cells (DCs), T cell infiltration, differentiation natural killer (NK) memory cells, thereby activating strong immune response. Consequently, it significantly inhibited both primary distant tumors, while also limiting lung summary, study proposed configuration-mediated transition strategy efficient immunotherapy, advancing frontiers organic agents (OPTAs) design synthesis.

Language: Английский

Citations

0