Silk Fibroin for CpG Oligodeoxynucleotide Delivery.

CpG oligodeoxynucleotides (ODNs) have attracted increasing attention as immunotherapeutic agents. However, efficient transfection of CpG ODNs into the immune cells remains a big challenge. In this study, for the first time, we reported that silk fibroin (SF) could function as an efficient carrier for CpG ODNs. A novel strategy was developed to prepare SF-CpG ODNs nanoparticles (NPs) based on self-assembly of SF. The as-prepared SF-CpG NPs were spherical in shape and were uniformly dispersed. SF-CpG NPs exhibited good stability and biocompatibility. SF-CpG NPs possessed significantly enhanced (7 folds) cellular uptake compared with CpG ODNs. Release of CpG ODNs from SF-CpG NPs was accelerated in environment-mimicking TLR9-localized endo/lysosome. SF-CpG NPs stimulated about four folds higher levels of immune cytokines and nitric oxide compared with CpG ODNs. Our results suggested that SF notably improved the CpG ODNs delivery. SF-CpG NPs have strong potential in immunotherapy.