Activation of invariant Natural Killer T lymphocytes in response to the α-galactosylceramide analogue KRN7000 encapsulated in PLGA-based nanoparticles and microparticles.

Abstract

Invariant Natural Killer T (iNKT) cells have potent immunostimulatory activities that could be exploited for human therapies. The high-affinity CD1d antigen α-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, 90nm) and microparticles instead of macroparticles (MPs, 715nm) 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.

• Authors: Elodie Macho Fernandez, Jiang Chang, Josette Fontaine, Emilie Bialecki, Fabien Rodriguez, Elisabeth Werkmeister, Vanessa Krieger, Christophe Ehret, Béatrice Heurtault, Sylvie Fournel, Benoit Frisch, Didier Betbeder, Christelle Faveeuw, François Trottein
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 423 Issue 1 Pg. 45-54 (Feb 14 2012) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 21575695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Clathrin
• Drug Carriers
• Galactosylceramides
• Interleukin-2
• Polylactic Acid-Polyglycolic Acid Copolymer
• Interleukin-4
• Polyglycolic Acid
• Lactic Acid
• Interferon-gamma
• KRN 7000

Topics

• Animals
• Antigen Presentation (immunology)
• Antineoplastic Agents (administration & dosage, immunology, pharmacology)
• Cell Proliferation (drug effects)
• Clathrin (metabolism)
• Coculture Techniques
• Dendritic Cells (drug effects, immunology, metabolism)
• Drug Carriers (chemistry)
• Endocytosis (drug effects, immunology)
• Galactosylceramides (administration & dosage, immunology, pharmacology)
• Interferon-gamma (blood, metabolism)
• Interleukin-2 (metabolism)
• Interleukin-4 (blood, metabolism)
• Killer Cells, Natural (immunology, metabolism)
• Lactic Acid (chemistry)
• Leukocytes, Mononuclear (drug effects, immunology, metabolism)
• Liver (cytology, immunology)
• Lymphocyte Activation (drug effects, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy, Electron, Transmission
• Microspheres
• Nanoparticles (chemistry)
• Natural Killer T-Cells (cytology, immunology, metabolism)
• Particle Size
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Spleen (cytology, drug effects, immunology)
• Static Electricity
• Surface Properties