The mRNA vaccines have become a transformative platform in medicine,with their success during the COVID-19 pandemic accelerating research in viral prevention and cancer therapy.Lipid nanoparticles(LNPs)enhance the sta...The mRNA vaccines have become a transformative platform in medicine,with their success during the COVID-19 pandemic accelerating research in viral prevention and cancer therapy.Lipid nanoparticles(LNPs)enhance the stability and efficacy of mRNA vaccines,but achieving an optimal balance between innate immune activation and mRNA expression is crucial for their effectiveness.Classical cationic lipids,although largely replaced by ionizable lipids due to concerns over excessive immunogenicity,have demonstrated potential in cancer immunotherapy by inducing strong immune responses.In this study,we investigated whether incorporating cationic lipids into mRNA-LNP formulations could enhance immunogenicity without requiring new lipid designs.We introduced varying proportions of cationic lipids into D-Lin-MC3-DMA and SM-102-based LNPs and evaluated their impact on innate immune activation,along with long-term humoral and cellular immune responses.Our results showed that in MC3-based LNPs,cationic lipids significantly improved anti-tumor efficacy,though slightly diminished long-term humoral and cellular immunity.In contrast,in SM-102-based LNPs,cationic lipids enhanced anti-tumor effects without negatively impacting long-term immunity.These findings suggest that adding cationic lipid as an additional component allows for the fine-tuning of mRNA-LNP immunogenicity,expanding the potential applications of mRNA vaccines and simplifying LNP design.展开更多
基金This work was supported by National Key Research and Development Program of China(grant No.2021YFC2302400)Major Program of the National Natural Science Foundation of China(grant Nos.T2394503 and T2394501)+2 种基金CAS Project for Young Scientists in Basic Research(grant No.YSBR-010)Key Project of the National Natural Science Foundation of China(grant No.32030062)IPE Project for Frontier Basic Research(grant No.QYJC2023-04)。
文摘The mRNA vaccines have become a transformative platform in medicine,with their success during the COVID-19 pandemic accelerating research in viral prevention and cancer therapy.Lipid nanoparticles(LNPs)enhance the stability and efficacy of mRNA vaccines,but achieving an optimal balance between innate immune activation and mRNA expression is crucial for their effectiveness.Classical cationic lipids,although largely replaced by ionizable lipids due to concerns over excessive immunogenicity,have demonstrated potential in cancer immunotherapy by inducing strong immune responses.In this study,we investigated whether incorporating cationic lipids into mRNA-LNP formulations could enhance immunogenicity without requiring new lipid designs.We introduced varying proportions of cationic lipids into D-Lin-MC3-DMA and SM-102-based LNPs and evaluated their impact on innate immune activation,along with long-term humoral and cellular immune responses.Our results showed that in MC3-based LNPs,cationic lipids significantly improved anti-tumor efficacy,though slightly diminished long-term humoral and cellular immunity.In contrast,in SM-102-based LNPs,cationic lipids enhanced anti-tumor effects without negatively impacting long-term immunity.These findings suggest that adding cationic lipid as an additional component allows for the fine-tuning of mRNA-LNP immunogenicity,expanding the potential applications of mRNA vaccines and simplifying LNP design.
