pH-sensitive PEG-coated hyper-branched β-d-glucan derivative as carrier for CpG oligodeoxynucleotide delivery

  • Carbohydr Polym. 2020 Oct 15;246:116621. doi: 10.1016/j.carbpol.2020.116621.
Yuting Su  1 Xiaojie Li  2 Ka Lung Lam  3 Peter C K Cheung  4
Affiliations
  • 1. School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: [email protected].
  • 2. Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, 518060, China. Electronic address: [email protected].
  • 3. School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: [email protected].
  • 4. School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: [email protected].
Abstract

β-d-glucan is a natural non-digestible polysaccharide that can be selectively recognized by recognition receptors such as Dectin-1 receptors, resulting in an emerging interest on exploring its capacity for carrying biological information to desired organs or cells. CpG oligodeoxynucleotide (ODN) has the potentiality to initiate an immune-stimulatory cascade via activating B cells inducing proinflammatory cytokines, which is conducive to immunotherapy and nucleic acid vaccine. Herein, we developed a pH-sensitive delivery system loading with CpG ODN by introducing poly-ethylenimine (PEI) to a hyperbranched β-d-glucan (HBB) and coating with poly-ethylene glycol (PEG) shell via acidic liable Schiff bond. This delivery system exhibited a favorable biocompatibility and facilitated the cellular uptake of CpG ODN at pH 6.8 with the possibility of having higher accumulation in acidic Cancer microenvironment. Furthermore, this carrier together with class B CpG ODN could enhance the secretion of cytokines including interleukin-6 and interferon-α as well as capable of interferon-α induction.

Keywords
CpG ODN; Cytokine induction; Delivery system; Immunotherapy; β-d-glucan.
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