Cleavable conjugation of CpG oligodeoxynucleotides onto microparticles for facile release and cytokine induction in macrophages

Abstract

The development of biomaterials for efficient intracellular delivery of the nucleic acid-based immune-stimulating molecule, CpG oligodeoxynucleotides (CpG), is crucial for their biological activity. In this study, we successfully fabricated polydopamine-coated porous poly(lactic-co-glycolic acid) microparticles (PPM) for the delivery of CpGs. After conjugation of CpGs to PPMs via cleavable disulfide linkages, CpGs were readily released from CpG-conjugated PPM (PPM-s–s-CpGs) in reductive conditions. Released CpGs exhibited significantly enhanced induction of two cytokines, TNF-α and IL-6, in RAW264.7 cells. GpC-conjugated PPMs showed negligible cytokine induction, whereas CpG-conjugated PPMs exhibited strong induction of the two cytokines in RAW264.7 cells. The PPM-s–s-CpGs can serve as immune-stimulating adjuvants to enhance the immune responses of vaccines.