Highly Efficient DNA Vaccine Based On Hydrolytic Cationic Ester Particles

DNA vaccines holds great potential for clinical applications as the next generation of vaccines, cationic polymers such as poly(ethylenimine) (PEI) which could efficiently condense negatively charged DNA molecules are commonly used for this purpose. However, PEI always bring high toxicity to the cells while they do not have the ability to unpack the DNA after entering the cells. Furthermore, when prepare DNA vaccine using PEI, materials such as PLGA which may cause the hydrolysis of DNA, and polystyrene which is non-degradable, are always needed to form particles. In this work, we used a convenient one-step method to prepare degradable particles with hydrolytic cationic ester. Before hydrolysis, the particles could efficiently condense DNA due to their positive surface charge, but after they are uptaken by the cells, they can be hydrolyzed to non-toxic zwitterionic polymers, consequently release the DNA and induce endosome escape. By tuning the particle sizes and composition, passive targeting to the macrophage cells with high transfection efficiency was achieved. These results indicate the particles presented in this work hold great potential in the field of DNA vaccination.