脂质体
阳离子脂质体
药物输送
化学
单核细胞
受体
聚糖
CD14型
细胞生物学
靶向给药
生物化学
生物
糖蛋白
免疫学
转染
有机化学
基因
作者
Rasmus Münter,Martin Bak,Mikkel E. Thomsen,Ladan Parhamifar,Allan Stensballe,Jens B. Simonsen,Kasper Kristensen,Thomas L. Andresen
标识
DOI:10.1016/j.ijpharm.2024.124129
摘要
Cationic liposomes specifically target monocytes in blood, rendering them promising drug-delivery tools for cancer immunotherapy, vaccines, and therapies for monocytic leukaemia. The mechanism behind this monocyte targeting ability is, however, not understood, but may involve plasma proteins adsorbed on the liposomal surfaces. To shed light on this, we investigated the biomolecular corona of three different types of PEGylated cationic liposomes, finding all of them to adsorb hyaluronan-associated proteins and proteoglycans upon incubation in human blood plasma. This prompted us to study the role of the TLR4 co-receptors CD44 and CD14, both involved in signalling and uptake pathways of proteoglycans and glycosaminoglycans. We found that separate inhibition of each of these receptors hampered the monocyte uptake of the liposomes in whole human blood. Based on clues from the biomolecular corona, we have thus identified two receptors involved in the targeting and uptake of cationic liposomes in monocytes, in turn suggesting that certain proteoglycans and glycosaminoglycans may serve as monocyte-targeting opsonins. This mechanistic knowledge may pave the way for rational design of future monocyte-targeting drug-delivery platforms.
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