Abstract

AbstractIn this short report, we demonstrate that liposomes bearing the Lewis X trisaccharide on the surface (“Awesosomes”) efficiently target human dendritic cells. We chose a glycolipid with Lewis X trisaccharide headgroup to facilitate the targeted liposome uptake via the DC-SIGN internalization pathway. While no uptake of Awesosomes was detected with wild-type human HEK293 cells, HEK293 cells transfected with human DC-SIGN internalized Awesosomes extensively. In samples of human blood-derived leukocytes, the extent of uptake of Awesosomes correlated with the expression of DC-SIGN, which is a dendritic cells marker. There was a marked difference in the uptake of Awesosomes and plain liposomes by DC-SIGN expressing dendritic cells. There was no difference in uptake of Awesosomes and plain liposomes by wt HEK293 cells or macrophages. These results indicate that Lewis X trisaccharide can “sweet-talk” dendritic cells into internalizing a delivery vehicle, and that Awesosomes are promising as “magic bullets” for specific delivery of drugs, antigens, or immunostimulatory molecules to human dendritic cells without influencing other cell types.

Highlights

  • Dendritic cells (DCs) are the most powerful antigen presenting cells

  • We demonstrate that liposomes bearing the Lewis X trisaccharide on the surface (“Awesosomes”) efficiently target human dendritic cells

  • We chose a glycolipid with Lewis X trisaccharide headgroup to facilitate the targeted liposome uptake via the DC-SIGN internalization pathway

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Summary

Introduction

Dendritic cells (DCs) are the most powerful antigen presenting cells. They are extremely potent in priming naïve T-cells (and have been designated the “nature’s adjuvants” [Steinman, 2007], and in inducing cytotoxic immune responses (CTL). DCs are capable of crosspresentation, the induction of a cytotoxic cell response against exogenously acquired antigen [Bevan, 1976]. This mode of CTLs induction against an exogenous antigen has been described only relatively recently and is extremely important for developing vaccines against certain pathogens including malaria, HIV, and TB [Winau, 2006], and against tumor cells. Targeted delivery of immunostimulants should decrease the likelihood of mounting a generalized inflammatory response; current adjuvants elicit a generalized inflammatory response, often leading to a number of side effects like swelling

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