Graphene oxide-chitosan nanocomposites for intracellular delivery of immunostimulatory CpG oligodeoxynucleotides.
CpG oligodeoxynucleotides (ODNs) activate innate and adaptive immune responses, and show strong potential as immunotherapeutic agents against various diseases. Benefiting from their unique physicochemical properties, graphene oxide (GO) has recently attracted great attention in nanomedicine. In this study, we developed a novel CpG ODNs delivery system based on GO-chitosan (GO-CS) nanocomposites. GO-CS nanocomposites were prepared by self-assembly of both components via electrostatic interactions. Compared with GO, GO-CS nanocomposites possessed smaller size, positive surface charge and lower cytotoxicity. CpG ODNs were loaded onto GO-CS nanocomposites via electrostatic interactions. GO-CS nanocomposites greatly improved the loading capacity and cellular uptake of CpG ODNs. GO-CS/CpG ODNs complexes further resulted in an enhanced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production compared with that of free CpG ODNs and GO/CpG ODNs complexes. Therefore, GO-CS nanocomposites can serve as efficient nanocarriers for enhancing the delivery efficiency of CpG ODNs.
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Huijie
H
Zhang
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Ting
T
Yan
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Sha
S
Xu
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Shini
S
Feng
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Dandi
D
Huang
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Morihisa
M
Fujita
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address: xdgao@jiangnan.edu.cn.
Xiao-Dong
XD
Gao
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D006108:Graphite / Q000138:chemical synthesis / Q000737:chemistry*; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D018625:Microscopy, Atomic Force; D053761:Nanocomposites / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D017550:Spectroscopy, Fourier Transform Infrared
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D006108:Graphite; D048271:Chitosan
Chitosan; CpG oligodeoxynucleotides; Cytokines; Drug delivery; Graphene oxide