title: Self-assembly of poly-adenine-tailed CpG oligonucleotide-gold nanoparticle nanoconjugates with immunostimulatory activity.
abstract: Synthetic unmethylated cytosine-guanine (CpG) oligodeoxynucleotides (CpG ODNs) possess high immunostimulatory activity and have been widely used as a therapeutic tool for various diseases including infection, allergies, and cancer. A variety of nanocarriers have been developed for intracellular delivery of CpG ODNs that are otherwise nonpermeable through the cellular membrane. For example, previous studies showed that gold nanoparticles (AuNPs) could efficiently deliver synthetic thiolated CpG ODNs into cultured cells and induce expression of proinflammatory cytokines. Nevertheless, the necessity of using thiolated CpG ODNs for the modification of AuNPs inevitably complicates the synthesis of the nanoconjugates and increases the cost. A new approach is demonstrated for facile assembly of AuNP-CpG nanoconjugates for cost-effective drug delivery. It is found that non-thiolated, diblock ODNs containing a CpG motif and a poly-adenine (polyA) tail can readily self-assemble on the surface of AuNPs with controllable and tunable density. Such nanoconjugates are efficiently delivered into RAW264.7 cells and induce immune response in a Toll-like receptor 9 (TLR9)-dependent manner. Under optimal conditions, polyA-CpG-AuNPs show significantly higher immunostimulatory activity than their thiolated counterpart. In addition, the immunostimulatory activity of CpG-AuNPs can be modulated by varying the length of the polyA tail. In vivo induction of immune responses in mice is demonstrated by using polyA-tailed CpG-AuNP nanoconjugates.
authors: Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
authors: Nan
authors: N
authors: Chen
authors: Min
authors: M
authors: Wei
authors: Yanhong
authors: Y
authors: Sun
authors: Fan
authors: F
authors: Li
authors: Hao
authors: H
authors: Pei
authors: Xiaoming
authors: X
authors: Li
authors: Shao
authors: S
authors: Su
authors: Yao
authors: Y
authors: He
authors: Lianhui
authors: L
authors: Wang
authors: Jiye
authors: J
authors: Shi
authors: Chunhai
authors: C
authors: Fan
authors: Qing
authors: Q
authors: Huang
mesh_terms: D000225:Adenine / Q000737:chemistry*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D051217:Toll-Like Receptor 9 / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D006046:Gold; D000225:Adenine
keywords: TLR-9; diblock oligonucleotides; gold nanoparticles; immunostimulatory activity; poly-adenine tails