CpG-induced immune responses via DNA micelles, gold nanoparticles, and liposomes

CpG oligodeoxynucleotides (CpG ODNs) are well-known adjuvants that induce innate immunity, particularly dendritic cell activation, by stimulating Toll-like receptor 9. However, the stimulatory efficacy of CpG ODNs is limited by their negative charge, which causes electrostatic repulsion from the cell membrane and hinders cellular uptake. In addition, CpG ODNs are rapidly degraded by nucleases under physiological conditions. To address these challenges, various nanoparticle (NP)-based delivery systems have been developed and applied across biomedical fields. Although various types of NPs have been utilized, the relationship between their physical properties and CpG delivery efficiency remains under investigation. In this study, we selected three commonly used and well-established nanocarriers-DNA micelles, gold nanoparticles (AuNPs), and liposomes-which differ in size and rigidity and are known for their effectiveness in drug delivery. We aim to evaluate and compare the in vivo delivery efficiency and immunostimulatory activity of these NPs when functionalized with CpG ODNs, thereby providing insights into how NP properties influence CpG-mediated immune activation.