This article was originally published here

ACS Nano. 2020 Aug 18. doi: 10.1021/acsnano.0c04188. Online ahead of print.

ABSTRACT

DNA vaccines are a promising cancer immunotherapy approach. However, effective delivery of DNA to antigen-presenting cells (e.g., dendritic cells (DCs)) for the induction of an adaptive immune response is limited. Conventional DNA delivery via intramuscular, intradermal, and subcutaneous injection by hypodermal needles shows low potency and immunogenicity. Here, we propose the enhanced cancer DNA vaccine by direct transfection to the high number of DCs recruited into the chemoattractant-loaded injectable mesoporous silica microrods (MSRs). Subcutaneous administration of the MSRs mixed with tumor-antigen coding DNA polyplexes resulted in DC recruitment in the macroporous space of the scaffold formed by the spontaneous assembly of high-aspect-ratio MSRs, thereby allowing for enhanced cellular uptake of antigen-coded DNA by host DCs. The MSR scaffolds delivering DNA vaccine trigger more robust DC activation, antigen-specific CD8+ T cell response, and Th1 immune response compared to the bolus DNA vaccine. Additionally, the immunological memory can be induced with a single administration of the vaccine. The combination of the vaccination and anti-programmed cell death-1 antibody significantly eliminates established lung metastasis. These results indicate that MSRs serve as a powerful platform for DNA vaccine delivery to DCs for effective cancer immunotherapy.

PMID:32808762 | DOI:10.1021/acsnano.0c04188



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