Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α.
BACKGROUND
Class B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules.


METHODS
For improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO(2) nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO(2) nanoparticles were prepared by coating SiO(2) nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da).


RESULTS
The capacity of the flake-shell SiO(2) nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO(2) nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO(2) nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO(2) nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO(2) nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO(2) nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO(2) nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO(2) nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.
Department of Medical Physics, Anna University, Chennai, India.
Yuvaraj
Y
Manoharan
Qingmin
Q
Ji
Tomohiko
T
Yamazaki
Shanmugavel
S
Chinnathambi
Song
S
Chen
Singaravelu
S
Ganesan
Jonathan P
JP
Hill
Katsuhiko
K
Ariga
Nobutaka
N
Hanagata
D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
C408982:CPG-oligonucleotide; D004337:Drug Carriers; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D012822:Silicon Dioxide; D011094:Polyethyleneimine