Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade DOI Creative Commons
Yu Chen,

Yu Guo,

Wen Cheng

et al.

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

Published: Nov. 26, 2024

Abstract Due to the inherent immunosuppression and immune evasion of cancer cells, combining photoimmunotherapy with checkpoint blockade leverages phototherapy enhancement, overcoming mutual limitations demonstrating significant anticancer potential. The main challenges include nonspecific accumulation agents, uncontrolled activation, drug carrier safety. Smart DNA nanospheres (NS) is developed targeted delivery controllable release photosensitizers agents achieve effective synergistic therapy minimize side effects. multifunctional NS incorporate a targeting module for programming aptamers, response i‐motif DNA/RNA hybrid sequences, therapeutic packaging PD‐L1 siRNA. navigate tumor site are sequentially activated by intracellular acid enzymes programmed death ligand 1 (PD‐L1) small interfering RNA (siRNA). Besides killing promotion, downregulate expression, alleviating tolerance evasion, thus enhancing response. These results indicate that significantly enhance antitumor responses, synergistically improve efficacy, reduce systemic toxicity. This study broadens application nanomaterials in precision therapy.

Language: Английский

Structure, function, signaling pathways and clinical therapeutics: The translational potential of STAT3 as a target for cancer therapy DOI
Dandan Shi,

Jiejing Tao,

Shuli Man

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189207 - 189207

Published: Nov. 1, 2024

Language: Английский

Citations

6
siRNA tackles cancer: Immune checkpoint inhibitors and siRNA combinations DOI Creative Commons
Andrew H. Coles

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102429 - 102429

Published: Jan. 6, 2025

Language: Английский

Citations

0
Lipid-siRNA Conjugates Targeting High PD-L1 Expression as Potential Novel Immune Checkpoint Inhibitors DOI Creative Commons

Rina Tansou,

Takanori Kubo, Haruka Nishida

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 293 - 293

Published: Feb. 15, 2025

Programmed death 1 ligand (PD-L1), an important immune checkpoint molecule, is mainly expressed on cancer cells and has been shown to exert immunosuppressive effect T-cell function by binding programmed cell (PD-1) T-cells. Recently, inhibitors using antibody drugs such as nivolumab atezolizumab have attracted attention. However, clinical challenges, including limitations the scope of their application, are yet be addressed. In this study, we developed a novel inhibitor that targets PD-L1 lipid-siRNA conjugates (lipid-siPDL1s). The inhibitory lipid-siPDL1s expression was evaluated found strongly suppress mRNA expression. Notably, exerted significantly stronger than unmodified siPDL1. Interestingly, inhibited despite stimulation interferon-gamma, which induced overexpression genes. These results suggest could used inhibitors.

Language: Английский

Citations

0
G0S2 Promotes PD-L1 Expression in Monocytes and Influences the Efficacy of PD-1 Inhibitors in Hepatocellular Carcinoma DOI Open Access
Xueming Du, Wenwen Zhang,

Sujuan Sun

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 448 - 448

Published: April 13, 2025

Background: Hepatocellular carcinoma (HCC) is a prevalent and highly lethal form of liver cancer, with limited effective treatment options, particularly in the advanced stages. Immunotherapy using PD-1 inhibitors has emerged as promising modality, yet substantial proportion patients exhibit resistance or fail to respond such therapies. This study aimed elucidate role G0/G1 Switch 2 (G0S2) regulating PD-L1 expression monocytes within HCC tumor microenvironment investigate its impact on efficacy inhibitors. Methods: Gene data among treated were obtained from single-cell sequencing database; immunohistochemistry was performed detect G0S2 cancer tissues adjacent non-tumorous patients; flow cytometry utilized analyze G0S2, PD-L1, CD206, CD14 PBMCs CD8+T cell proliferation IFN-γ secretion used evaluate knockdown. Results: Utilizing patients, we identified that significantly elevated non-responders (NR) compared responders (R) inhibitor therapy. The immunohistochemical analysis confirmed higher levels tissues, while revealed increased CD206 peripheral blood mononuclear cells (PBMCs) NR R healthy controls. functional experiments involving knockdown THP-1 monocyte line resulted significant reduction concomitant increase production. Conclusions: These findings indicate facilitates upregulation monocytes, thereby suppressing T activity contributing against HCC. high offers non-invasive easily detectable biomarker for predicting Consequently, targeting may enhance responsiveness immunotherapy providing new avenue optimizing strategies improving patient outcomes.

Language: Английский

Citations

0
Local CpG-Stat3 siRNA treatment improves antitumor effects of immune checkpoint inhibitors DOI Creative Commons
Chunyan Zhang, Rui Huang,

Lyuzhi Ren

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2024, Volume and Issue: 35(4), P. 102357 - 102357

Published: Oct. 9, 2024

Language: Английский

Citations

3
Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade DOI Creative Commons
Yu Chen,

Yu Guo,

Wen Cheng

et al.

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

Published: Nov. 26, 2024

Abstract Due to the inherent immunosuppression and immune evasion of cancer cells, combining photoimmunotherapy with checkpoint blockade leverages phototherapy enhancement, overcoming mutual limitations demonstrating significant anticancer potential. The main challenges include nonspecific accumulation agents, uncontrolled activation, drug carrier safety. Smart DNA nanospheres (NS) is developed targeted delivery controllable release photosensitizers agents achieve effective synergistic therapy minimize side effects. multifunctional NS incorporate a targeting module for programming aptamers, response i‐motif DNA/RNA hybrid sequences, therapeutic packaging PD‐L1 siRNA. navigate tumor site are sequentially activated by intracellular acid enzymes programmed death ligand 1 (PD‐L1) small interfering RNA (siRNA). Besides killing promotion, downregulate expression, alleviating tolerance evasion, thus enhancing response. These results indicate that significantly enhance antitumor responses, synergistically improve efficacy, reduce systemic toxicity. This study broadens application nanomaterials in precision therapy.

Language: Английский

Citations

1