Orchestrating antigen delivery and presentation efficiency in lymph node by nanoparticle shape for immune response.

Area of Science:

• Immunology
• Nanotechnology
• Vaccine Development

Background:

• Activating immune responses in lymph nodes (LNs) is crucial for nanoparticle-based vaccines to control tumors.
• The role of nanovaccine carrier physical properties in antigen capture, lymphatic delivery, antigen presentation, and immune response within LNs remains unclear.

Purpose of the Study:

• To investigate how different gold nanoparticle (AuNP) shapes (cages, rods, stars) affect antigen delivery, immune cell activation, and vaccine efficacy.
• To explore shape-dependent strategies for prophylactic and therapeutic cancer vaccines.

Main Methods:

• Fabrication of size-matched gold nanoparticles (AuNPs) with distinct shapes: cages, rods, and stars.
• Loading AuNPs with tumor antigen to create nanovaccines.
• Evaluation of antigen capture, lymphatic transport, antigen presentation in LNs, and subsequent humoral and cellular immune responses.

Main Results:

• Star-shaped AuNPs demonstrated superior antigen epitope capture and retention.
• Nanovaccine shape influenced lymphatic drainage and LN localization (rods/stars to follicles, cages to paracortex).
• Star-shaped nanovaccines induced potent humoral immunity (CD4+ T helper and B cell cooperation), preventing tumor growth.
• Cage-shaped nanovaccines promoted CD8+ T cell immunity (via peptide-MHC I presentation) and showed strong therapeutic efficacy with PD-1 inhibition.

Conclusions:

• Nanoparticle shape is a critical determinant of antigen delivery, presentation, and immune response outcomes in LNs.
• Distinct nanovaccine designs are necessary for effective prophylactic (humoral immunity) and therapeutic (cellular immunity) applications.
• Findings provide a basis for rationally designing nanovaccines with shape-specific immune-modulating properties.