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Viral Nanoparticles for In vivo Tumor Imaging

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Modular core-shell polymeric nanoparticles mimicking viral structures for vaccination.

Bo Lou¹, Ans De Beuckelaer², Eger Boonstra¹

¹Department of Pharmaceutics, Utrecht Institute for Pharmaceutical science, Utrecht University, 3584CG Utrecht, the Netherlands.

Journal of Controlled Release : Official Journal of the Controlled Release Society

|November 15, 2018

Summary

Researchers developed virus-mimicking nanoparticles (VMPs) that effectively deliver antigens and RNA to stimulate strong immune responses. These novel VMPs show promise as a flexible platform for advanced vaccines against infectious diseases and cancer.

Keywords:

Click chemistry Nanoparticles TLR7/8 Vaccine adjuvant Virus mimicking structure

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Area of Science:

Nanotechnology and Materials Science
Immunology and Vaccine Development
Polymer Chemistry

Background:

Protein-based vaccines offer potential for treating infectious diseases and cancer.
A key challenge is developing efficient antigen delivery systems to stimulate cytotoxic T-lymphocyte (CTL) responses.
Mimicking viral structures is a promising strategy for vaccine design.

Purpose of the Study:

To construct novel virus-mimicking particles (VMPs) for enhanced vaccine development.
To evaluate the immunogenicity and efficacy of these VMPs in stimulating CTL and humoral immune responses.

Main Methods:

Synthesized cationic polymers with azide or bicyclo[6.1.0]nonyne (BCN) groups to bind single-stranded RNA (PolyU), forming a polyplex core.
Conjugated azide-modified ovalbumin (OVA) antigen and BCN-modified mannosylated/galactosylated polymer to the RNA core via disulfide bonds using click chemistry, creating a core-shell structure.
Characterized VMPs for size, surface charge, and colloidal stability; assessed cellular uptake, DC activation, MHC I Ag presentation in vitro, and immune responses in vivo.

Main Results:

Generated stable, 200 nm VMPs with a negative surface charge.
Mannosylated VMPs (VMP-Man) exhibited 5x higher uptake by dendritic cells (DCs) than galactosylated VMPs (VMP-Gal).
VMP-Man demonstrated enhanced DC activation, MHC I antigen presentation, and elicited strong OVA-specific CTL and humoral immune responses in mice.

Conclusions:

Modular core-shell polymeric nanoparticles effectively mimic viral structures for vaccine delivery.
VMP-Man significantly outperforms adjuvanted protein subunit vaccines in inducing robust and durable immune responses.
These VMPs represent a versatile platform for developing personalized vaccines against various diseases.