2. Academic Validation
  3. Chitosan derivative composite nanoparticles as adjuvants enhance the cellular immune response via activation of the cGAS-STING pathway

Chitosan derivative composite nanoparticles as adjuvants enhance the cellular immune response via activation of the cGAS-STING pathway

  • Int J Pharm. 2023 Mar 16;122847. doi: 10.1016/j.ijpharm.2023.122847.
Zhi Zhao 1,  Yue Peng 2,  Xueao Shi 1,  Kai Zhao 3
Affiliations

Affiliations

  • 1 Institute of Nanobiomaterials and Immunology & Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Life Science, Taizhou University, Taizhou, Zhejiang 318000, China; Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Science, Heilongjiang University, Harbin, Heilongjiang 150080, China.
  • 2 Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Science, Heilongjiang University, Harbin, Heilongjiang 150080, China.
  • 3 Institute of Nanobiomaterials and Immunology & Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Life Science, Taizhou University, Taizhou, Zhejiang 318000, China; Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Science, Heilongjiang University, Harbin, Heilongjiang 150080, China. Electronic address: zybin395@126.com.
PMID: 36933583 DOI: 10.1016/j.ijpharm.2023.122847
Abstract

Chitosan and its derivatives are widely used in vaccine adjuvants and delivery systems. Vaccine antigens encapsulated in or conjugated onto N-2-hydroxypropyl trimethyl ammonium chloride chitosan/N,O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) induce strong cellular, humoral, and mucosal immune responses, but the mechanism of action is not fully understood. Therefore, the purpose of this study was to explore the molecular mechanism of composite NPs by upregulating the cGAS-STING signalling pathway to enhance the cellular immune response. We showed that the N-2-HACC/CMCS NPs could be taken up by RAW264.7 cells and produced high levels of IL-6, IL-12p40, and TNF-α. The N-2-HACC/CMCS NPs activated BMDCs, promoted Th1 responses, and enhanced the expression of cGAS, TBK1, IRF3, and STING, as further demonstrated by qRT-PCR and western blotting. Moreover, the NP-induced expression of I-IFNs, IL-1β, IL-6, IL-10 and TNF-α in macrophages was closely related to cGAS-STING. These findings provide a reference for chitosan derivative nanomaterials as vaccine adjuvants and delivery systems and demonstrate that N-2-HACC/CMCS NPs can engage the STING-cGAS pathway to trigger the innate immune response.

Keywords

Chitosan quaternary ammonium salt nanoparticles; cGAS-STING pathway; immune adjuvant; immune efficacy; nanocarrier and delivery.

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