Hollow Aluminum Hydroxide Modified Silica Nanoadjuvants with Amplified Immunotherapy Effects through Immunogenic Cell Death Induction and Antigen Release

Small. 2022 Aug;18(34):e2202462. doi: 10.1002/smll.202202462. Epub 2022 Jul 27.

Abstract

In spite of the widespread application of vaccine adjuvants in various preventive vaccines at present, the existing adjuvants are still hindered by weak cellular immunity responses in therapeutic cancer vaccines. Herein, a hollow silica nanoadjuvant containing aluminum hydroxide spikes on the surface (SiAl) is synthesized for the co-loading of chemotherapeutic drug doxorubicin (Dox) and tumor fragment (TF) as tumor antigens (SiAl@Dox@TF). The obtained nanovaccines show significantly elevated anti-tumor immunity responses thanks to silica and aluminum-based composite nanoadjuvant-mediated tumor antigen release and Dox-induced immunogenic cell death (ICD). In addition, the highest frequencies of dendritic cells (DCs), CD4+ T cells, CD8+ T cells, and memory T cells as well as the best mice breast cancer (4T1) tumor growth inhibitory are also observed in SiAl@Dox@TF group, indicating favorable potential of SiAl nanoadjuvants for further applications. This work is believed to provide inspiration for the design of new-style nanoadjuvants and adjuvant-based cancer vaccines.

Keywords: cancer vaccine; cellular immunity; immunogenic cell death; immunotherapy; nanoadjuvant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Aluminum Hydroxide / metabolism
  • Animals
  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines*
  • Cell Line, Tumor
  • Dendritic Cells / metabolism
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Immunogenic Cell Death
  • Immunotherapy
  • Mice
  • Silicon Dioxide

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Aluminum Hydroxide
  • Silicon Dioxide
  • Doxorubicin