期刊
PHARMACEUTICS
卷 12, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics12121138
关键词
cancer vaccination; liposome; targeting; GM3; macrophage; CD169; Siglec-1; sialoadhesin; T cells
资金
- NWO ZonMW [TOP 91218024]
- Phospholipid Research Center
- Dutch Cancer Society [VU2016-10449]
Despite promising progress in cancer vaccination, therapeutic effectiveness is often insufficient. Cancer vaccine effectiveness could be enhanced by targeting vaccine antigens to antigen-presenting cells, thereby increasing T-cell activation. CD169-expressing splenic macrophages efficiently capture particulate antigens from the blood and transfer these antigens to dendritic cells for the activation of CD8(+) T cells. In this study, we incorporated a physiological ligand for CD169, the ganglioside GM3, into liposomes to enhance liposome uptake by CD169(+) macrophages. We assessed how variation in the amount of GM3, surface-attached PEG and liposomal size affected the binding to, and uptake by, CD169(+) macrophages in vitro and in vivo. As a proof of concept, we prepared GM3-targeted liposomes containing a long synthetic ovalbumin peptide and tested the capacity of these liposomes to induce CD8(+) and CD4(+) T-cell responses compared to control liposomes or soluble peptide. The data indicate that the delivery of liposomes to splenic CD169(+) macrophages can be optimized by the selection of liposomal constituents and liposomal size. Moreover, optimized GM3-mediated liposomal targeting to CD169(+) macrophages induces potent immune responses and therefore presents as an interesting delivery strategy for cancer vaccination.
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