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Self-Assembly of Poly-Adenine-Tailed CpG Oligonucleotide-Gold Nanoparticle Nanoconjugates with Immunostimulatory Activity

Authors

  • Nan Chen,

    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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  • Min Wei,

    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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  • Yanhong Sun,

    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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  • Fan Li,

    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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  • Hao Pei,

    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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  • Xiaoming Li,

    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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  • Shao Su,

    1. Key Laboratory for Organic Electronics & Information Displays (KLOEID), Institute of Advanced Materials (IAM), School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, Nanjing, China
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  • Yao He,

    1. Institute of Functional Nano and Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, China
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  • Lianhui Wang,

    1. Key Laboratory for Organic Electronics & Information Displays (KLOEID), Institute of Advanced Materials (IAM), School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, Nanjing, China
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  • Jiye Shi,

    1. UCB Pharma, UK
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  • Chunhai Fan,

    Corresponding author
    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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  • Qing Huang

    Corresponding author
    1. Division of Physical Biology & Bioimaging Center, Shanghai Sychrotron Radiation Facility (SSRF), Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China
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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.

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