Mechanisms of Selective Monocyte Targeting by Liposomes Functionalized with a Cationic, Arginine-Rich Lipopeptide

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Abstract

Stimulation of monocytes with immunomodulating agents can harness the immune system to treat a long range of diseases, including cancers, infections and autoimmune diseases. To this end we aimed to develop a monocyte-targeting delivery platform based on cationic liposomes, which can be utilized to deliver immunomodulators and thus induce monocyte-mediated immune responses while avoiding off-target side-effects. The cationic liposome design is based on functionalizing the liposomal membrane with a cholesterol-anchored tri-arginine peptide (TriArg). We demonstrate that TriArg liposomes can target monocytes with high specificity in both human and murine blood and that this targeting is dependent on the content of TriArg in the liposomal membrane. In addition, we show that the mechanism of selective monocyte targeting involves the CD14 co-receptor, and selectivity is compromised when the TriArg content is increased, resulting in complement-mediated off-target uptake in granulocytes. The presented mechanistic findings of uptake by peripheral blood leukocytes may guide the design of future drug delivery systems utilized for immunotherapy.
Original languageEnglish
JournalActa Biomaterialia
Volume144
Pages (from-to)96-108
ISSN1742-7061
DOIs
Publication statusPublished - 2022

Keywords

  • Cationic liposome
  • Immunotherapy
  • CD14
  • Complement
  • Monocyte

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