Publication Type Journal Article
Title Rational design of nanoparticles towards targeting antigen-presenting cells and improved T cell priming
Authors Eva Zupancic Caterina Curato Maria Paisana C. Rodrigues Ziv Porat A. Viana Carlos A. M. Afonso Joao Pinto Rogerio Gaspar Joao N. Moreira Ronit Satchi-Fainaro Steffen Jung Helena F. Florindo
Groups
Journal JOURNAL OF CONTROLLED RELEASE
Year 2017
Month July
Volume 258
Number
Pages 182-195
Abstract Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination with the engraftment of CD4(+) and CD8(+) T cells, carrying a transgenic OVA-responding T cell receptor (TCR), to trace and characterize the activation of antigenspecific CD4(+) and CD8(+) lymph node T cells upon NP vaccination. Accordingly, the phenotype and frequency of immune cell stimulation induced by the NP loaded with OVA, isolated or in combination with synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were characterized. DC-NP interactions increased with incubation time, presenting internalization values between 50 and 60\% and 30-40\%, in vitro and in vivo, respectively. Interestingly, animal immunization with antigen-adsorbed NP upregulated major histocompatibility complex (MHC) class II (MHCII), while NP entrapping the antigen upregulated MHCI, suggesting a more efficient cross-presentation. On the other hand, rather surprisingly, the surfactant used in the NP formulation had a major impact on the activation of antigen presenting cells (APC). In fact, DC collected from lymph nodes of animals immunized with NP prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed significantly higher levels of CD86, MHCI and MHCII. In addition, those NP prepared with PVA and co-entrapping OVA and the toll-like receptor (TLR) ligand CpG, induced the most profound antigen-specific T cell response, by both CD4(+) and CD8(+) T cells, in vivo. Overall, our data reveal the impact of NP composition and surface properties on the type and extension of induced immune responses. Deeper understanding on the NP-immune cell crosstalk can guide the rational development of nano-immunotherapeutic systems with improved and specific therapeutic efficacy and avoiding off-target effects.
DOI http://dx.doi.org/10.1016/j.jconrel.2017.05.014
ISBN
Publisher
Book Title
ISSN 0168-3659
EISSN 1873-4995
Conference Name
Bibtex ID ISI:000403886400017
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