A biodegradable lipid-enveloped nanoparticle containing a poly(P-amino-ester) core was developed for delivery of mRNA vaccines, based on the ability of the core polymer to disrupt endosomes. Messenger RNA (mRNA) was adsorbed via electrostatic interactions onto the surface of nanoparticles incorporating a cationic lipid. Particles carrying mRNA were internalized by dendritic cells (DCs) and mRNA was released into the cytosol of DCs with minimal cytotoxicity and translated into encoded protein in vitro. Particles loaded with mRNA administered intradermally in mice also led to the expression of a reporter protein in vivo. The expressed antigen can then be processed via classical MHC-Class I pathways to activate CD8~+ cytotoxic T cell immunity.
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