Uptake Kinetics Of Liposomal Formulations of Differing Charge Influences Development of in Vivo Dendritic Cell Immunotherapy

Noémi Anna Nagy,Charlotte Castenmiller,Fernando Lozano Vigario,Rinske Sparrius,Toni M.M Van Capel,Aram M De Haas,Yvette Van Kooyk,Ronald Van Ree,Sander W Tas,Teunis B.H Geijtenbeek,Wim Jiskoot,Bram Slütter,Esther C De Jong

doi:10.1016/j.xphs.2022.01.022

Abstract

Dendritic cells (DCs) control adaptive immunity and are therefore attractive for in vivo targeting to either induce immune activation or tolerance, depending on disease. Liposomes, nanoparticles comprised of a lipid bi-layer, provide a nanoplatform for loading disease-relevant antigen, adjuvant and DC-targeting molecules simultaneously. However, it is yet not fully understood how liposomal formulations affect uptake by DCs and DC function. Here, we examined monocyte-derived DC (moDC) and skin DC uptake of six different liposomal formulations, together with their DC-modulating effect. Contrary to literature, we show using imaging flow cytometry that anionic or neutral liposomes are taken up more efficiently than cationic liposomes by moDCs, or by skin DCs after intradermal injection. None of the formulations yielded significant modulation of DC function as determined by the upregulation of maturation markers and cytokine production. These results suggest that anionic liposomes would be more suitable as vaccine carriers for a dermal application.

Highlights

Dendritic cells (DCs) are considered important targets for novel immunotherapies due to their crucial role as orchestrators of both tolerogenic and immunogenic adaptive responses.[1,2] Ex vivo DC vaccination is an approved treatment against various forms of cancer.[1]
We present a systematic analysis comparing uptake and adjuvant effects of six differing liposomal formulations on human monocyte-derived DC (moDC) and skin DCs
With the aid of imaging flow cytometry, we clearly show that neutrally or negatively charged liposomes are more efficiently taken up compared to cationic liposomes DPTAP and DOTAP

Summary

Introduction

Dendritic cells (DCs) are considered important targets for novel immunotherapies due to their crucial role as orchestrators of both tolerogenic and immunogenic adaptive responses.[1,2] Ex vivo DC vaccination is an approved treatment against various forms of cancer.[1] Recent studies on several autoimmune conditions have borrowed the approach, replacing tumor antigens and immunogenic adjuvants with auto-antigens and tolerogenic adjuvants.[3] ex vivo DC vaccination is a costly, cumbersome method that can only be applied in a patient's tailor-made fashion. As an alternative DC-focused strategy, in vivo targeting holds promising potential. With this approach, DCs can be reached in their natural niche without external manipulation. Nanostructures with a lipid bi-layer, are biocompatible and suitable vehicles for loading DC-targeting and modulating compounds.[4]

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Results

Conclusion