BN nanospheres functionalized with mesoporous silica for enhancing CpG oligodeoxynucleotides-mediated cancer immunotherapy

CpG oligodeoxynucleotides (CpG ODNs) possess strong immunostimulatory activity, which hold great promise in cancer immunotherapy. However, their therapeutic efficacy are largely limited due to the nuclease degradation and poor cellular internalization. Efficiently delivering CpG ODNs into target cells is crucial to improve their therapeutic efficacy. Boron nitride nanospheres (BNNS) possessed advantage as carriers for CpG ODNs. However, their poor aqueous dispersity and low CpG ODNs loading capacity became a big obstacle for further applications. Herein, we developed amino group grafted, mesoporous silica (MS)-functionalized BNNS as novel nanovectors for CpG ODNs delivery. Modification of BNNS with MS significantly improved the dispersity of BNNS and CpG ODNs loading. BNNS@MS-NH2 exhibited no cytotoxicity and enhanced the delivery of CpG ODNs into macrophages. BNNS@MS-NH2/CpG ODNs complexes triggered enhanced immunostimulation and induced higher amount of cytokines. Most importantly, BNNS@MS-NH2/CpG ODNs complexes induced bifurcated cytokines, which simultaneously simulated the secretion of IL-6, TNF-α and IFN-α. In contrast, CpG ODNs and BNNS/CpG ODNs complexes could not. Result of transwell plate assay suggested that BNNS@MS-NH2/CpG ODNs complexes were more effective in inhibiting cancer cells growth. Taken together, our findings provide a promising strategy for enhancing CpG ODNs-mediated cancer immunotherapy.