Dendritic Mesoporous Silica Nanoparticle Adjuvants Modified with Binuclear Aluminum Complex: Coordination Chemistry Dictates Adjuvanticity

Angew Chem Int Ed Engl. 2020 Oct 26;59(44):19610-19617. doi: 10.1002/anie.202006861.

Abstract

Aluminum-containing adjuvants used in vaccine formulations suffer from low cellular immunity, severe aggregation, and accumulation in the brain. Conventional aluminosilicates widely used in the chemical industry focus mainly on acidic sites for catalytic applications, but they are rarely used as adjuvants. Reported here is an innovative "ligand-assisted steric hindrance" strategy to create a high density of six-coordinate VI Al-OH groups with basicity on dendritic mesoporous silica nanoparticles as new nanoadjuvants. Compared to four-coordinate IV Al-modified counterparts, VI Al-OH-rich aluminosilicate nanoadjuvants enhance cellular delivery of antigens and provoke stronger cellular immunity. Moreover, the aluminum accumulation in the brain is more reduced than that with a commercial adjuvant. These results show that coordination chemistry can be used to control the adjuvanticity, providing new understanding in the development of next-generation vaccine adjuvants.

Keywords: adjuvants; aluminum; coordination chemistry; mesoporous materials; surface chemistry.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Immunologic / toxicity
  • Aluminum / chemistry
  • Aluminum / pharmacology
  • Aluminum / toxicity
  • Aluminum Silicates / chemistry
  • Aluminum Silicates / pharmacology*
  • Aluminum Silicates / toxicity
  • Animals
  • Antigens / immunology
  • B-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Coordination Complexes / toxicity
  • Female
  • Lymphocyte Activation / drug effects
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Ovalbumin / immunology
  • Porosity
  • RAW 264.7 Cells
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / pharmacology*
  • Silicon Dioxide / toxicity

Substances

  • Adjuvants, Immunologic
  • Aluminum Silicates
  • Antigens
  • Coordination Complexes
  • Silicon Dioxide
  • Ovalbumin
  • Aluminum