Vitamin E Scaffolds of pH-Responsive Lipid Nanoparticles as DNA Vaccines in Cancer and Protozoan Infection

📖 Top 20% JournalMar 5, 2020Molecular pharmaceutics

pH-Responsive Vitamin E–Based Lipid Nanoparticles for DNA Vaccines Against Cancer and Protozoan Infection

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Abstract

Liposomal nanoparticles (LNPs) containing ssPalmE demonstrated higher gene expression activity after subcutaneous administration.

Immunization with ssPalmE-LNPs encapsulating plasmid DNA encoding ovalbumin induced significant antitumor effects.
Immunization with ssPalmE-LNPs containing plasmid DNA for profilin resulted in notable antiprotozoan effects.
In draining lymph nodes, ssPalmE-LNPs were primarily taken up by macrophages and a smaller fraction by dendritic cells.
Transient deletion of CD169 macrophages unexpectedly increased the activity of the DNA vaccine.
These findings suggest that ssPalmE-LNPs are promising carriers for DNA vaccines.

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DNA vaccinations are promising strategies for treating diseases that require cellular immunity (i.e., cancer and protozoan infection). Here, we report on the use of a liposomal nanocarrier (lipid nanoparticles (LNPs)) composed of an SS-cleavable and pH-activated lipidlike material (ssPalm) as an in vivo DNA vaccine. After subcutaneous administration, the LNPs containing an ssPalmE, an ssPalm with vitamin E scaffolds, elicited a higher gene expression activity in comparison with the other LNPs composed of the ssPalms with different hydrophobic scaffolds. Immunization with the ssPalmE-LNPs encapsulating plasmid DNA that encodes ovalbumin (OVA, a model tumor antigen) or profilin (TgPF, a potent antigen of) induced substantial antitumor or antiprotozoan effects, respectively. Flow cytometry analysis of the cells that had taken up the LNPs in draining lymph nodes (dLNs) showed that the ssPalmE-LNPs were largely taken up by macrophages and a small number of dendritic cells. We found that the transient deletion of CD169macrophages, a subpopulation of macrophages that play a key role in cancer immunity, unexpectedly enhanced the activity of the DNA vaccine. These data suggest that the ssPalmE-LNPs are effective DNA vaccine carriers, and a strategy for avoiding their being trapped by CD169macrophages will be a promising approach for developing next-generation DNA vaccines. Toxoplasma gondii + +

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