Back to Search
Start Over
Activation of invariant Natural Killer T lymphocytes in response to the α-galactosylceramide analogue KRN7000 encapsulated in PLGA-based nanoparticles and microparticles
- Source :
- International Journal of Pharmaceutics, International Journal of Pharmaceutics, 2012, 423 (1), pp.45-54. ⟨10.1016/j.ijpharm.2011.04.068⟩, International Journal of Pharmaceutics, Elsevier, 2012, 423 (1), pp.45-54. ⟨10.1016/j.ijpharm.2011.04.068⟩
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- International audience; 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.
- Subjects :
- Male
Liver cytology
Pharmaceutical Science
Lymphocyte Activation
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Mice
chemistry.chemical_compound
0302 clinical medicine
Polylactic Acid-Polyglycolic Acid Copolymer
Mice, Knockout
Antigen Presentation
Drug Carriers
0303 health sciences
biology
Chemistry
Endocytosis
Microspheres
3. Good health
Cell biology
Killer Cells, Natural
PLGA
Liver
030220 oncology & carcinogenesis
CD1D
Surface Properties
Static Electricity
Antineoplastic Agents
Galactosylceramides
Interferon-gamma
03 medical and health sciences
Microscopy, Electron, Transmission
Antigen
In vivo
Animals
Lactic Acid
Particle Size
[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials
Cell Proliferation
030304 developmental biology
T-cell receptor
Dendritic Cells
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
Clathrin
Coculture Techniques
In vitro
Mice, Inbred C57BL
Immunology
Leukocytes, Mononuclear
biology.protein
Interleukin-2
Nanoparticles
Natural Killer T-Cells
Interleukin-4
Polyglycolic Acid
Spleen
Subjects
Details
- Language :
- English
- ISSN :
- 03785173
- Database :
- OpenAIRE
- Journal :
- International Journal of Pharmaceutics, International Journal of Pharmaceutics, 2012, 423 (1), pp.45-54. ⟨10.1016/j.ijpharm.2011.04.068⟩, International Journal of Pharmaceutics, Elsevier, 2012, 423 (1), pp.45-54. ⟨10.1016/j.ijpharm.2011.04.068⟩
- Accession number :
- edsair.doi.dedup.....108948231e85cdb78136864d5f5c59c5