Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 423, Issue 1, Pages 45-54Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2011.04.068
Keywords
KRN; PLGA-based particles; Dendritic cells; iNKT cells; Cytokines
Categories
Funding
- Inserm
- CNRS
- University of Lille Nord de France
- University of Strasbourg
- Pasteur Institute of Lille
- Institut National du Cancer (INCa) [R08046EE/RPT08003EEA]
- Ministere de l'Enseignement Superieur et de la Recherche
- Institut National du Cancer
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Invariant Natural Killer T (iNKT) cells have potent immunostimulatory activities that could be exploited for human therapies. The high-affinity CD1d antigen alpha-galactosylceramide analogue KRN7000 (KRN) activates a cascade of anti-tumor effector cells and clinical studies have already had some initial success. To improve the efficacy of the treatment, strategies that aim to vectorize KRN would be valuable. In this study, we intended to characterize and compare the effect of KRN encapsulated in poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs, 90 nm) and microparticles instead of macroparticles (MPs, 715 nm) on the iNKT cell response. Our data show that whatever the size of the particles, vectorized KRN induced potent primary activation of iNKT cells in vitro and in vivo. We show that endocytosis of PLGA-based particles by dendritic cells is mediated by a clathrin-dependent manner and that this event is important to stimulate iNKT cells. Finally, we report that KRN vectorized in NPs and MPs exhibited different behaviours in vivo in terms of iNKT cell expansion and responsiveness to a recall stimulation. Collectively, our data validate the concept that KRN encapsulated in PLGA-based particles can be used as delivery systems to activate iNKT cells in vitro and in vivo. (C) 2011 Elsevier B.V. All rights reserved.
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