Homotypic targeting of immunomodulatory nanoparticles for enhanced peripheral and central immunity

Objectives Synthetic oligodeoxynucleotides (ODNs) that contain unmethylated cytosine-phosphate-guanine (CpG) motifs serve as immune adjuvants in disease treatment. However, the poor cell permeability and safety concerns limit their medical applications, and biocompatible strategies for efficient delivery of functional CpG ODNs are highly desirable. Materials and Methods Self-assembled, cell membrane-coated CpG nanoparticles (NP) are prepared, and their physicochemical properties are characterized. The uncoated and membrane-coated CpG NP are compared for their biocompatibility, cellular uptake kinetics, endocytic pathways, subcellular localization, and immunostimulatory activities in macrophages and microglia. Results Macrophage- or microglia-derived cell membrane camouflaging alters the endocytic pathways of CpG NP, promotes their targeted delivery to the cells with homologous membrane, ensures their endosomal localization, and enhances their immunomodulatory effects. Conclusions We design a type of biomimetic NP consisting of self-assembled CpG NP core and cell membrane shell, and demonstrate its advantages in the modulation of peripheral and central immune cells. Our study provides a new strategy for the application of CpG ODNs.

Automated summary

In this study, a biomimetic nanoparticle consisting of a self-assembled CpG NP core and cell membrane shell was designed, showing advantages in modulating peripheral and central immune cells. This new strategy provides targeted delivery and immunomodulatory effects for CpG ODNs in disease treatment.