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Review
. 2021 Mar;38(3):473-478.
doi: 10.1007/s11095-021-03015-x. Epub 2021 Mar 3.

Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives

Zimei Wu  1 , Tonglei Li  2
Affiliations
Review

Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives

Zimei Wu et al. Pharm Res. 2021 Mar.

Abstract

The COVID-19 pandemic has left scientists and clinicians no choice but a race to find solutions to save lives while controlling the rapid spreading. Messenger RNA (mRNA)-based vaccines have become the front-runners because of their safety profiles, precise and reproducible immune response with more cost-effective and faster production than other types of vaccines. However, the physicochemical properties of naked mRNA necessitate innovative delivery technologies to ferry these 'messengers' to ribosomes inside cells by crossing various barriers and subsequently induce an immune response. Intracellular delivery followed by endosomal escape represents the key strategies for cytoplasmic delivery of mRNA vaccines to the target. This Perspective provides insights into how state-of-the-art nanotechnology helps break the delivery barriers and advance the development of mRNA vaccines. The challenges remaining and future perspectives are outlined.

Keywords: endosomal escape; intracellular delivery; mRNA vaccines; nanomedicines; ribosome.

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Figures

Fig. 1
Fig. 1
Simplified schematic representation of cellular uptake and intracellular trafficking of naked mRNA versus LNP encapsulated mRNA. 1) mRNA is loaded into various nanoparticles, 2) mRNA nanoconstruct or naked mRNA is internalized via different endocytosis pathways (clathrin- and caveolae-mediated, or lipid raft raft), 3) mRNA nanoconstruct undergoes endosomal escape leading to cargo release into cytosol and ribosome, 4) naked mRNA ended in lysosomes and subsequently degraded with only a small proportion escaped into the cytosol, and 5) extracellular unprotected mRNA undergoes enzymatic degradation.
See this image and copyright information in PMC

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