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Updated: May 15, 2025
Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation
Published on: September 16, 2018
Dynamic DNA-Based Nanoadjuvants for TLR9 Clustering and Innate Immune Activation in Dendritic Cells
Zhaoyue Lv1,2, Xiaocui Guo2,3, Rui Zhang1
1Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, College of Chemistry and Materials, Fudan University, Shanghai 200438, P.R. China.
A novel DNA nanoadjuvant self-assembles in lysosomes to cluster toll-like receptor 9 (TLR9), enhancing innate immunity and antitumor responses. This smart system promises advancements in vaccine adjuvants and cancer immunotherapy.
Area of Science:
- Immunology
- Nanotechnology
- Biochemistry
Background:
- Toll-like receptor (TLR) clustering is crucial for innate immunity, but precise control over receptor assembly is difficult.
- Developing effective methods for regulating TLR clustering is essential for advancing immune-based therapies.
Purpose of the Study:
- To develop a dynamic, DNA-based nanoadjuvant for controlled TLR9 clustering and enhanced innate immune activation.
- To investigate the mechanism of nanoadjuvant assembly and its impact on lysosomal function and immune response.
Main Methods:
- A DNA-based nanoadjuvant integrating CpG oligonucleotides and acid-responsive DNA sequences was constructed using a cascade hybridization chain reaction.
- Nanoadjuvant assembly was triggered by lysosomal acidity via cytosine protonation-induced i-motif formation.
- The effects of nanoadjuvant assembly on lysosomal acidity, hydrolase activity, and TLR9 clustering were analyzed.
Main Results:
- The nanoadjuvant self-assembled into large aggregates within lysosomes, reducing acidity and enhancing retention.
- Aggregated nanoadjuvants promoted prolonged TLR9 ligand-receptor interactions, leading to efficient TLR9 clustering.
- This clustering effectively induced dendritic cell maturation, cytokine secretion, and T-cell proliferation, resulting in significant antitumor immunity.
Conclusions:
- The developed DNA nanoadjuvant offers a novel, stimulus-responsive system for manipulating receptor assembly and potentiating innate immune responses.
- This approach demonstrates significant potential for applications in vaccine adjuvants and cancer immunotherapy by enhancing antitumor immunity.
