Polyethyleneimine-functionalized boron nitride nanospheres as efficient carriers for enhancing the immunostimulatory effect of CpG oligodeoxynucleotides.
CpG oligodeoxynucleotides (ODNs) stimulate innate and adaptive immune responses. Thus, these molecules are promising therapeutic agents and vaccine adjuvants against various diseases. In this study, we developed a novel CpG ODNs delivery system based on polyethyleneimine (PEI)-functionalized boron nitride nanospheres (BNNS). PEI was coated on the surface of BNNS via electrostatic interactions. The prepared BNNS-PEI complexes had positive zeta potential and exhibited enhanced dispersity and stability in aqueous solution. In vitro cytotoxicity assays revealed that the BNNS-PEI complexes with concentrations up to 100 μg/mL exhibited no obvious cytotoxicity. Furthermore, the positively charged surface of the BNNS-PEI complexes greatly improved the loading capacity and cellular uptake efficiency of CpG ODNs. Class B CpG ODNs loaded on the BNNS-PEI complexes enhanced the production of interleukin-6 and tumor necrosis factor-α from peripheral blood mononuclear cells compared with CpG ODNs directly loaded on BNNS. Contrary to the free CpG ODNs or CpG ODNs directly loaded on BNNS, class B CpG ODNs loaded on the BNNS-PEI complexes induced interferon-α simultaneously. PEI coating may have changed the physical form of class B CpG ODNs on BNNS, which further affected their interaction with Toll-like receptor 9 and induced interferon-α. Therefore, BNNS-PEI complexes can be used to enhance the immunostimulatory effect and therapeutic activity of CpG ODNs and the treatment of diseases requiring interleukin-6, tumor necrosis factor-α, and interferon-α.
The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People's Republic of China.
Huijie
H
Zhang
The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People's Republic of China.
Shini
S
Feng
The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People's Republic of China.
Ting
T
Yan
Department of Physics and Materials Science, City University of Hong Kong, Kowlong, Hong Kong SAR, People's Republic of China.
Chunyi
C
Zhi
The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People's Republic of China.
Xiao-Dong
XD
Gao
Biomaterials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Ibaraki, Japan ; Nanotechnology Innovation Station, National Institute for Materials Science, Ibaraki, Japan.
Nobutaka
N
Hanagata
D000276:Adjuvants, Immunologic / Q000737:chemistry; D001896:Boron Compounds / Q000737:chemistry*; D004337:Drug Carriers; D006801:Humans; D007107:Immune System; D016898:Interferon-alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D054118:Nanospheres / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D001896:Boron Compounds; C408982:CPG-oligonucleotide; D004337:Drug Carriers; C508600:IL6 protein, human; D016898:Interferon-alpha; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; C439524:TNF protein, human; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; C017282:boron nitride; D011094:Polyethyleneimine
CpG oligodeoxynucleotide; boron nitride nanosphere; cytokine; immunostimulatory effect; polyethyleneimine