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Multivalent Co-assembly of LL37-CpG nanoparticles: Enhanced immune response through activating multiple cell
Yushuang Wei1, Wenwen Li1, Rong Xu2,1
1Songshan Lake Materials Laboratory, Dongguan, 523808, Guangdong, China.
Materials Today. Bio
|July 7, 2025
Summary
The human antimicrobial peptide LL37 helps assemble CpG oligonucleotides (CpG ODNs) into nanoparticles, enhancing cellular uptake and boosting immune responses for potential vaccine adjuvants and therapeutics.
Area of Science:
- Immunology
- Biotechnology
- Nanomedicine
Background:
- The human antimicrobial peptide LL37 is crucial for immune regulation and elevated in chronic inflammatory diseases.
- Understanding LL37's mechanism is key for developing immune adjuvants and therapeutics.
- CpG oligonucleotides (CpG ODNs) are clinically relevant immune adjuvants.
Purpose of the Study:
- To investigate how LL37 facilitates the assembly of CpG ODNs into nanoparticles.
- To determine the cellular uptake mechanisms and immune activation potential of LL37-CpG nanoparticles.
- To explore the therapeutic applications of LL37-CpG complexes.
Main Methods:
- LL37 was used to assemble CpG ODNs into nanoparticles (NPs) with controlled size and zeta potential.
- Cellular uptake pathways (receptor-mediated macropinocytosis, clathrin-mediated endocytosis) were analyzed.
- TNF-α production in macrophages was measured to assess immune activation via lysosomal TLR9.
Main Results:
- LL37 assembled CpG ODNs into charge ratio-dependent nanoparticles.
- LL37-CpG NPs utilized macropinocytosis and LL37-mediated membrane penetration for enhanced cellular uptake.
- LL37-CpG NP internalization significantly boosted TNF-α production in macrophages (>3.5-fold) via lysosomal TLR9.
Conclusions:
- LL37-CpG nanoparticle assembly enhances cellular uptake and immune cell activation.
- This mechanism provides a novel approach for modulating immune responses using peptide-CpG ODN complexes.
- LL37-CpG NPs show promise as vaccine adjuvants and for immune modulation in disease treatment.
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