Hollow Mesoporous Silica Nanoparticles with Extra-Large Mesopores for Enhanced Cancer Vaccine

ACS Appl Mater Interfaces. 2020 Aug 5;12(31):34658-34666. doi: 10.1021/acsami.0c09484. Epub 2020 Jul 28.

Abstract

Owing to the limitations of conventional cancer therapies, cancer immunotherapy has emerged for the prevention of cancer recurrence. To provoke adaptive immune responses that are antigen-specific, it is important to develop an efficient antigen delivery system that can enhance the activation and maturation of the dendritic cells (DCs) in the human body. In this study, we synthesize hollow mesoporous silica nanoparticles with extra-large mesopores (H-XL-MSNs) based on a single-step synthesis from core-shell mesoporous silica nanoparticles with a core composed of an assembly of iron oxide nanoparticles. The hollow void inside the mesoporous silica nanoparticles with large mesopores allows a high loading efficiency of various model proteins of different sizes. The H-XL-MSNs are coated with a poly(ethyleneimine) (PEI) solution to provide an immune adjuvant and change the surface charge of the particles for loading and slow release of a model antigen. An in vitro study using a cancer vaccine based on the PEI-coated H-XL-MSNs with the loading of the model antigen showed an enhanced activation of the DCs. An in vivo study demonstrated that the resulting cancer vaccine increased the antigen-specific cytotoxic T cells, enhanced the suppression of tumor growth, and improved the survival rate after challenging cancer to mice. These findings suggest that these hollow MSNs with extra-large pores can be used as excellent antigen carriers for immunotherapy.

Keywords: cancer immunotherapy; cytotoxic T cells; dendritic cells; hollow silica nanoparticles; mesoporous silica nanoparticles.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology
  • Mice
  • Nanoparticles / chemistry*
  • Particle Size
  • Porosity
  • Silicon Dioxide / chemistry*
  • Surface Properties
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Silicon Dioxide