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Updated: May 10, 2026
Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Selectively targeting the toll-like receptor 9 (TLR9)--IRF 7 signaling pathway by polymer blend particles
Helen C Chen1, Xi Zhan, Kenny K Tran
1Department of Chemical Engineering, University of Washington, 253 Benson Hall, Box 351750, Seattle, WA 98195, USA.
Abstract:
Signaling through toll-like receptor 9 (TLR9) has been exploited for cancer therapy. The stimulation of TLR9 leads to two bifurcating signaling pathways - NF-κB-dependent pro-inflammatory cytokines pathway and IRF-7-dependent type I interferons (IFNs) pathway. In this study, we employ polymer blend particles to present the synthetic ligand, CpG oligonucleotides (CpG ODNs), to TLR9. The polymer blend particles are made from the blend of pH-insensitive and pH-sensitive copolymer. By tailoring the composition of the pH-sensitive polymer, CpG ODNs are presented to TLR9 in a way that only activates the IRF-7 signaling pathway. CpG ODNs have been used for cancer therapy in both preclinical and clinical studies. The selective activation of IRF-7 could potentially enhance the apoptosis of tumor cells and immunological control of tumor progression without inadvertently activating NF-κB-dependent oncogenesis.
Insights
Researchers developed polymer blend particles to deliver CpG oligonucleotides (CpG ODNs) for cancer therapy. This method selectively activates the IRF-7 pathway, potentially enhancing tumor apoptosis and immune control without promoting oncogenesis.
Area of Science:
- Immunology
- Materials Science
- Oncology
Background:
- Toll-like receptor 9 (TLR9) signaling is a target for cancer therapy.
- TLR9 activation bifurcates into NF-κB and IRF-7 dependent pathways.
- Uncontrolled NF-κB activation can promote oncogenesis.
Purpose of the Study:
- To develop a method for selective TLR9 pathway activation.
- To enhance cancer apoptosis and immune control.
- To avoid NF-κB-mediated oncogenesis.
Main Methods:
- Utilized polymer blend particles composed of pH-insensitive and pH-sensitive copolymers.
- Incorporated CpG oligonucleotides (CpG ODNs) as synthetic TLR9 ligands.
- Tailored pH-sensitive polymer composition to control CpG ODN release and TLR9 activation.
Main Results:
- Achieved selective activation of the IRF-7 signaling pathway.
- Demonstrated a method to present CpG ODNs to TLR9 via tailored polymer particles.
- Avoided inadvertent activation of the NF-κB pathway.
Conclusions:
- Selective IRF-7 activation via polymer-delivered CpG ODNs shows promise for cancer therapy.
- This approach may enhance tumor apoptosis and immunological tumor control.
- Potential to mitigate risks associated with NF-κB-dependent oncogenesis in cancer treatment.
