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PLGA Nanoparticles Modified with a TNFα Mimicking Peptide, Soluble Leishmania Antigens and MPLA Induce T Cell Priming In Vitro via Dendritic Cell Functional Differentiation

Margaronia et al., European Journal of Pharmaceutics and Biopharmaceutics (2016) - PMID: 27235727

Product(s) used in this publication:  Custom Peptide Synthesis

Abstract:

Poly(lactide-co-glycolide) nanoparticles (PLGA NPs) represent a new approach for vaccine delivery due to their ability to be taken up by phagocytes and to activate immune responses. In the present study PLGA NPs were surface-modified with a TNFα mimicking peptide, and encapsulated soluble Leishmania antigens (sLiAg) and MPLA adjuvant. The synthesized PLGA NPs exhibited low cytotoxicity levels, while surface-modified NPs were more efficiently taken up by dendritic cells (DCs). The prepared nanoformulations induced maturation and functional differentiation of DCs by elevating co-stimulatory molecule levels and stimulating IL-12 and IL-10 production. Sensitized DCs promoted T cell priming, characterized by the development of mixed T cell subsets differentiation expressing Th lineage-specific transcriptional factors and cytokine genes. Moreover, PLGA NPs were biocompatible, while they were located in lymphoid organs and taken up by phagocytic cells. Our results suggest that surface-modified PLGA NPs encapsulating sLiAg and MPLA could be considered as an effective vaccine candidate against leishmaniasis.

Copyright © 2016 Elsevier B.V. All rights reserved.

KEYWORDS:

Cytokine expression; Dendritic cells; Leishmania; Maturation; PLGA NPs; T cell priming

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