Stealth mRNA nanovaccines to control lymph node trafficking

J Control Release. 2024 Oct:374:325-336. doi: 10.1016/j.jconrel.2024.08.018. Epub 2024 Aug 22.

Abstract

mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine.

Keywords: (zwitterionics; Delivery systems; Nanoparticles; Reactogenicity); cancer; mRNA.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Female
  • Humans
  • Lymph Nodes* / immunology
  • Mice
  • Mice, Inbred C57BL*
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / chemistry
  • Nanovaccines
  • RNA, Messenger* / administration & dosage
  • Vaccines / administration & dosage
  • Vaccines / immunology
  • mRNA Vaccines

Substances

  • RNA, Messenger
  • mRNA Vaccines
  • Vaccines
  • Cancer Vaccines
  • Nanovaccines