Spleen-Targeted mRNA Delivery by Amphiphilic Carbon Dots for Tumor Immunotherapy

In recent years, the application of mRNA vaccine based tumor immunotherapy invigorated anti-tumor therapy. However, the low efficiency of mRNA delivery and the lack of targeting ability in vivo are the major obstacles to achieving highly efficient immunotherapy. In this work, we report a chemical library of amphiphilic carbon dots (ACDs) and the synthesized ACDs were applied to mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can smoothly bind with mRNA to form ACDs@mRNA nanocomplexes, and the fluorescent properties of the ACDs afforded the nanoparticles with bio-imaging ability. By screening of the ACDs, O12-Tta-CDs were found to have optimal mRNA transfection efficiency and the ability of spleen-targeted delivery. In addition, O12-Tta-CDs can well transfect the immune cells and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Furthermore, O12-Tta-CDs@OVA-mRNA was successfully applied to inhibit tumor growth, and more specific T-cell infiltration was observed in spleen and tumors of mice after treatment in the E.G7-OVA tumor model. Besides, O12-Tta-CDs@OVA-mRNA also achieved a good therapeutic effect in tumor recurrence inhibition and tumor prophylactic experiments. This study provided a new direction for the design of mRNA vectors, which is promising in tumor immunotherapy.

Automated summary

In recent years, the application of mRNA vaccine based tumor immunotherapy has shown potential in improving anti-tumor therapy. However, efficient delivery of mRNA and targeted delivery in vivo remain major challenges. To address this, researchers have developed amphiphilic carbon dots (ACDs) for mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can bind with mRNA and form nanocomplexes, allowing for bio-imaging. Through screening, O12-Tta-CDs showed optimal mRNA transfection efficiency and spleen-targeted delivery. Furthermore, O12-Tta-CDs promoted immune cell transfection, dendritic cell maturation, and antigen presentation, leading to successful tumor growth inhibition and enhanced T-cell infiltration in mice. These findings offer promising strategies for mRNA vector design and tumor immunotherapy.