期刊
JOURNAL OF CONTROLLED RELEASE
卷 291, 期 -, 页码 135-146出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2018.10.028
关键词
Liposomes; Tolerance; Atherosclerosis; Regulatory T cells; Clq; Vaccination
资金
- Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation
- Dutch Federation of University Medical Centers
- Netherlands Organization for Health Research and Development
- Royal Netherlands Academy of Sciences [CVON2011-19]
Atherosclerosis is the predominant underlying pathology of many types of cardiovascular disease and is one of the leading causes of death worldwide. It is characterized by the retention of oxidized low-density lipoprotein (ox-LDL) in lipid-rich macrophages (foam cells) in the intima of arteries. Autoantigens derived from oxLDL can be used to vaccinate against atherosclerosis. However, a major challenge is the induction of antigen-specific Tregs in a safe and effective way. Here we report that liposomes containing the anionic phospholipid 1,2distearoyl-sn-glycero-3-phosphoglycerol (DSPG) induce Tregs that are specific for the liposomes' cargo. Mechanistically, we show a crucial role for the protein corona that forms on the liposomes in the circulation, as uptake of DSPG-liposomes by antigen-presenting cells is mediated via complement component lq (Clq) and scavenger receptors (SRs). Vaccination of atherosclerotic mice on a western-type diet with DSPG-liposomes encapsulating an LDL-derived peptide antigen significantly reduced plaque formation by 50% and stabilized the plaques, and reduced serum cholesterol concentrations. These results indicate that DSPG-liposomes have potential as a delivery system in vaccination against atherosclerosis.
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