Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 12, Issue -, Pages 1251-1264Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S125866
Keywords
cationic liposome; nanoparticle; vaccine; cross-presentation; lysosome
Funding
- NIH [1R01-AI127070, 1R01-EB022563, UL1TR000433]
- China Scholarship Fund
- Melanoma Research Alliance [348774]
- NSF CAREER Award [1553831]
- DoD/CDMRP Peer Reviewed Cancer Research Program [W81XWH-16-1-0369]
- Directorate For Engineering [1553831] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys [1553831] Funding Source: National Science Foundation
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Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation -the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide: MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3 beta-[N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2- dioleoyl-3- trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross- presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross- priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross- presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials.
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