Tripartite siRNA micelles as controlled delivery systems for primary dendritic cells

Abstract

Dendritic cells (DCs) are key cells in immunology that are able to stimulate or inhibit the immune response. RNA interference has appeared of great interest to modulate the expression of immunogenic or tolerogenic molecules. In our study, pH-sensitive polyion complex micelles based on a double-hydrophilic block copolymer and poly-l-lysine were formulated to entrap a small interfering RNA (siRNA). We show that siRNA-loaded micelles were cytotolerant and efficiently endocytosed by DCs. siRNA targeting eGFP, used as model siRNA, was released into the cytosol following endocytosis of the micelles and the silencing of eGFP expression was observed in DC isolated from transgenic mice.

Our results underscore the potential of pH-sensitive polyion complex micelles to formulate therapeutic siRNA for DC engineering in order to maintain the homeostasis of the immune response.

Keywords:

• Dendritic cells
• endosomal escape
• gene silencing
• pH-sensitive polyion complex micelles
• siRNA
• tripartite association

Acknowledgments

The authors are willing to thank Montpellier RIO imaging platform to have put confocal laser scanning microscopy and fluorescence microscopy at our disposal and P. Peralta for technical support.

Declaration of interest: The authors report no conflicts of interest.