Anionic 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) liposomes induce antigen-specific regulatory T cells and prevent atherosclerosis in mice

JOURNAL OF CONTROLLED RELEASE

卷:291

Article

Benne, Naomi¹  van Duijn, Janine¹  Vigario, Fernando Lozano¹  Leboux, Romain J. T.¹  van Veelen, Peter²  Kuiper, Johan¹  Jiskoot, Wim¹  Stutter, Bram¹ 

[1] Leiden Acad Ctr Drug Res, Divison BioTherapeut, Leiden, Netherlands

[2] Leiden Univ, Ctr Prote & Metabol, Med Ctr, Leiden, Netherlands

关键词: Liposomes;    Tolerance;    Atherosclerosis;    Regulatory T cells;    Clq;    Vaccination;   

DOI  :  10.1016/j.jconrel.2018.10.028

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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