Issue 27, 2023

Novel α-mannose-functionalized poly(β-amino ester) nanoparticles as mRNA vaccines with increased antigen presenting cell selectivity in the spleen

Abstract

mRNA vaccination has emerged as a prominent therapy for the future of medicine. Despite the colossal advance in this technology and worldwide efficacy proof (ca. COVID vaccines), mRNA carriers still lack cell/tissue specificity, leading to possible side effects, and reduced efficacy among others. Herein we make use of the ubiquitous affinity of antigen-presenting cells (APC)s for glycosides to achieve specific targeting. To achieve this goal, we designed a new generation of α-mannosyl functionalized oligopeptide-terminated poly(β-aminoester). Fine formulation of these polymers with mRNA resulted in nanoparticles decorated with surface-exposed α-mannoses with sizes around 180 nm and positive surface charge. Notably, these particles maintained their properties after freeze-drying and subsequent redispersion. Finally, our mRNA carriers preferentially targeted and transfected APCs in vitro and in vivo. In conclusion, we demonstrated, at a preclinical level, that the mannose functionalization enables more selective targeting of APCs and, thus, these polymer and nanoparticles are candidates for a new generation of mRNA immunotherapy vaccines.

Graphical abstract: Novel α-mannose-functionalized poly(β-amino ester) nanoparticles as mRNA vaccines with increased antigen presenting cell selectivity in the spleen

Supplementary files

Article information

Article type
Paper
Submitted
22 mar 2023
Accepted
23 may 2023
First published
14 iyn 2023
This article is Open Access
Creative Commons BY-NC license

J. Mater. Chem. B, 2023,11, 6412-6427

Novel α-mannose-functionalized poly(β-amino ester) nanoparticles as mRNA vaccines with increased antigen presenting cell selectivity in the spleen

N. González-Ríos, M. Artigues, M. Guerra-Rebollo, A. Planas, S. Borrós, M. Faijes and C. Fornaguera, J. Mater. Chem. B, 2023, 11, 6412 DOI: 10.1039/D3TB00607G

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