LMU Researchers Develop Hybrid Nanocarrier System for Inhalable mRNA Vaccines
核心洞察
Researchers at LMU have developed a novel hybrid polymer nanocarrier system combining PLGA (搜索) and PBAEs (搜索) for effective inhalable mRNA vaccine delivery.
The hybrid nanoparticles successfully overcome lung barriers, penetrate airway mucus, and efficiently transfect immune cells for robust immune activation.
The system demonstrates superior robustness during aerosolization compared to clinically approved lipid nanoparticles, maintaining higher transfection efficiency after nebulization.
A research team at Ludwig-Maximilians-Universität München (LMU) has developed a breakthrough delivery system for inhalable mRNA vaccines that could revolutionize mucosal vaccination approaches. The novel hybrid polymer nanocarriers, combining poly(lactic-co-glycolic acid) (PLGA (搜索)) and poly(β-amino esters) (PBAEs (搜索)), successfully overcome multiple biological barriers in the lungs while maintaining superior performance during aerosolization.
Overcoming Critical Delivery Challenges
The research, led by Professor Olivia M. Merkel, Chair of Drug Delivery at LMU and published in Cell Biomaterials, addresses fundamental challenges in pulmonary vaccine delivery. "Effective mucosal vaccination via inhalation requires carrier systems that can penetrate airway mucus while protecting the fragile RNA molecules they carry," explains Merkel.
The hybrid system operates through a spatiotemporally coordinated mechanism that enables the nanocarriers to escape from endosomes and efficiently transfect mRNA into immune cells. This process is critical for presenting antigens on cell surfaces and achieving robust immune activation.
Superior Performance in Human Lung Models
The LMU team demonstrated that their hybrid nanoparticles efficiently transfect targeted immune system cells and support both antigen presentation and immune cell maturation. Significantly, the particles successfully crossed the mucus barrier and enabled mRNA expression in ex vivo human precision-cut lung slices, representing a highly relevant human lung model for testing vaccine delivery systems.
Enhanced Stability During Aerosolization
A key advantage of the new system lies in its robustness during the nebulization process. "A major advantage of the new system is its robustness during aerosolization," says Merkel. After vibrating-mesh nebulization, the PLGA (搜索)/PBAE nanocarriers retained higher transfection efficiency than clinically approved lipid nanoparticles, highlighting their superior suitability for inhaled vaccine applications.
Implications for Next-Generation Vaccines
The hybrid platform represents a significant advancement in data-driven polymer design for vaccine delivery. "Our findings show that data-driven polymer design can address multiple delivery barriers simultaneously. This hybrid platform offers a promising alternative to lipid nanoparticles for next-generation pulmonary mRNA vaccines," Merkel noted.
The study, supported by the Bavarian Research Foundation and the European Research Council (ERC), makes an important contribution to developing safe, effective, and patient-friendly mucosal vaccines. The research team's approach demonstrates how combining different polymer systems can create synergistic effects that overcome individual limitations of existing delivery platforms.