Virus-inspired Ganoderma lucidum polysaccharide-functionalized adjuvant with pseudo-zwitterionic interface for
Xu-Han Liu1, Zhe Zhai2, Ling-Ling Tao2
1Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Institute for Inheritance-based Innovation of Chinese Medicine, Marshall Laboratory of Biomedical Engineering, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China..
Carbohydrate Polymers
|April 7, 2026
Summary
We developed virus-inspired nanoparticles that overcome the mucus barrier for effective intranasal vaccines. These nanoparticles enhance antigen uptake and boost mucosal and systemic immunity against respiratory infections.
Area of Science:
- Biomaterials Science
- Immunology
- Nanotechnology
Background:
- Intranasal vaccination offers a promising route for respiratory infection prevention but faces challenges due to the mucus barrier.
- Traditional delivery systems often struggle to balance mucosal adhesion and penetration, limiting vaccine efficacy.
Purpose of the Study:
- To engineer a virus-inspired hybrid nanoparticle (GHNP) that overcomes the mucus barrier for enhanced intranasal vaccine delivery.
- To optimize the nanoparticle's properties for improved mucosal penetration and antigen uptake.
- To evaluate the immunostimulatory effects and immune response elicited by the novel nanoparticle system.
Main Methods:
- Developed Ganoderma lucidum polysaccharide (GLP)-functionalized hybrid nanoparticles (GHNP) with a cationic polymer/lipid core.
- Tuned GLP surface modification density to achieve optimal mucus interaction and penetration, identifying a 1:24 GLP-to-HNP mass ratio.
- Assessed mucus penetration, antigen uptake by dendritic cells and macrophages, and immune responses (sIgA, IgG) in a murine intranasal immunization model.
Main Results:
- Optimized GHNP(1/24) nanoparticles (∼104 nm, +27 mV) exhibited enhanced mucus penetration via a virus-mimetic pseudo-zwitterionic interface.
- Achieved significant improvements in antigen uptake: 79-fold in dendritic cells and 25-fold in macrophages under mucin barrier conditions.
- Demonstrated potent immunostimulatory activity via TLR2/4 activation, leading to elevated bronchoalveolar sIgA (1.5-fold) and serum IgG (1.6-fold) compared to antigen alone.
Conclusions:
- The developed modular nanoparticle platform offers a tunable, dual-functional strategy for advanced mucosal vaccine design.
- GHNP technology successfully bridges structural biomimetics and carbohydrate immunoengineering to overcome mucus barrier limitations.
- This approach surpasses traditional delivery systems by simultaneously addressing mucosal penetration and immunostimulation for improved vaccine efficacy.
