PLGA nanoparticles modified with a TNFα mimicking peptide, soluble Leishmania antigens and MPLA induce T cell priming in vitro via dendritic cell functional differentiation

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• 作者：Maritsa Margaroni^a ; ^b ; Maria Agallou^a ; Katerina Kontonikola^c ; ^d ; Konstantina Karidi^d ; Olga Kammona^d ; Costas Kiparissides^c ; ^d ; Catherine Gaitanaki^b ; Evdokia Karagouni^a ; ^{ekaragouni@pasteur.gr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PLGA NPs ; Leishmania ; Dendritic cells ; Maturation ; T cell priming ; Cytokine expression
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：105
• 期：Complete
• 页码：18-31
• 全文大小：2759 K

文摘

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.