Development of Functionalized Nanoparticles for Vaccine Delivery to Dendritic Cells: A Mechanistic Approach

Silva, Joana M.; Vandermeulen, Gaëlle; Oliveira, Vanessa G.; Pinto, Sandra N.; Rodrigues, Catarina A. B.; Salgado, Ana; Afonso, Carlos A. M.; Viana, Ana S.; Jérôme, Christine; Silva, Liana C.; Graça, Luís; Préat, Véronique; Florindo, Helena F.

doi:10.2217/nnm.14.135

Cited by 38 publications

(26 citation statements)

References 41 publications

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“…Moreover, no significant differences were observed even after 48 h of incubation with 1000 μg/mL of nanoparticles. A similar profile was achieved by Silva et al (2014) with cell viabilities were higher than 70 % after 48 h of incubation of PLGA nanoparticles with JAWSII cells. 29 These results show that the manufacturing process led to nanoparticles which residual amounts of organic solvent and surfactant do not affect the viability of targeted cells.…”

Section: Dendritic Cell Viability In the Presence Of Nanoparticlessupporting

confidence: 73%

Optimization of protein loaded PLGA nanoparticle manufacturing parameters following a quality-by-design approach

et al. 2016

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Section: Dendritic Cell Viability In the Presence Of Nanoparticlessupporting

confidence: 73%

Optimization of protein loaded PLGA nanoparticle manufacturing parameters following a quality-by-design approach

et al. 2016

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“…These different metabolic pathways must influence antigen presentation and need to be considered in the development of a vaccine formulation [30]. For example, Silva et al (2014) showed that macropinocytosis, clathrin-mediated endocytosis, and caveolin-and lipid raftdependent endocytosis are involved in the internalization of mannose-grafted PLGA nanoparticles by murine bone marrow-derived DCs. Their formulation allowed the antigen to be presented through both the MHC class I and II pathways, thus inducing a complete immune response [31].…”

Section: Discussionmentioning

confidence: 99%

“…The absence of nanoparticlesand MPLA-mediated toxicity in cells at the concentrations used (250 μg/mL for NPs and between 6.12 μg/mL and 50 μg/mL for MPLA) was in accordance with the literature. Indeed, studies performed with A549 human lung epithelial cells showed that concentrations of PLA-NPs ranging from 2 to 200 μg/mL or concentrations of PLGA-NPs ranging from 0.01 to 4 mg/mL had no effect on cell viability according to analyses performed with MTT and LDH assays [31,32]. Concerning MPLA, Ismaili et al found no cytotoxic effects on human monocyte-derived DCs even at 100 μg/mL [19].…”

Section: Discussionmentioning

confidence: 99%

In vitro evaluations on canine monocyte-derived dendritic cells of a nanoparticles delivery system for vaccine antigen against Echinococcus granulosus

et al. 2020

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Since dogs play a central role in the contamination of humans and livestock with Echinococcus granulosus, the development of an effective vaccine for dogs is essential to control the disease caused by this parasite. For this purpose, a formulation based on biodegradable polymeric nanoparticles (NPs) as delivery system of recombinant Echinococcus granulosus antigen (tropomyosin EgTrp) adjuved with monophosphoryl lipid A (MPLA) has been developed. The obtained nanoparticles had a size of approximately 200 nm in diameter into which the antigen was correctly preserved and encapsulated. The efficiency of this system to deliver the antigen was evaluated in vitro on canine monocyte-derived dendritic cells (cMoDCs) generated from peripheral blood monocytes. After 48 h of contact between the formulations and cMoDCs, we observed no toxic effect on the cells but a strong internalization of the NPs, probably through different pathways depending on the presence or not of MPLA. An evaluation of cMoDCs activation by flow cytometry showed a stronger expression of CD80, CD86, CD40 and MHCII by cells treated with any of the tested formulations or with LPS (positive control) in comparison to cells treated with PBS (negative control). A higher activation was observed for cells challenged with EgTrp-NPs-MPLA compared to EgTrp alone. Formulations with MPLA, even at low ratio of MPLA, give better results than formulations without MPLA, proving the importance of the adjuvant in the nanoparticles structure. Moreover, autologous T CD4+ cell proliferation observed in presence of cMoDCs challenged with EgTrp-NPs-MPLA was higher than those observed after challenged with EgTrp alone (p<0.05). These first results suggest that our formulation could be used as an antigen delivery system to targeting canine dendritic cells in the course of Echinococcus granulosus vaccine development.

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“…A key advantage of particulate vectors relative to other non-viral gene delivery systems is their superior in vivo stability. The principal types of polymers studied in this context include those made of poly(lactide) (PLA; reviewed in [ 99 ]), poly(lactide-co-glycolide) (PLGA; reviewed in [ 99 , 100 , 102 ]), polyorthoesters [ 103 ], polystyrene (PS) [ 104 , 105 ] and poly(ε-caprolactone) [ 106 ]. Of these, PLGA has been studied most extensively in terms of its capacity to stimulate APCs.…”

Section: Micro-and Nano-particulate Dna Delivery Vectorsmentioning

confidence: 99%

Polymer-Based DNA Delivery Systems for Cancer Immunotherapy

David

Golani-Armon

2016

Advances in Delivery Science and Technology

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The use of gene delivery systems for the expression of antigenic proteins is an established means for activating a patient's own immune system against the cancer they carry. Since tumor cells are poor antigen-presenting cells, crosspresentation of tumor antigens by dendritic cells (DCs) is essential for the generation of tumor-specifi c cytotoxic T-lymphocyte responses. A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specifi c, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular traffi cking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection effi ciency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter summarizes the physicochemical properties and biological information on polymer-based non-viral vectors used for targeting DCs, and discusses the main challenges for successful in vivo gene transfer into DCs.

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Development of Functionalized Nanoparticles for Vaccine Delivery to Dendritic Cells: A Mechanistic Approach

Abstract: The developed nanoparticles might drive antigens to be presented through MHC class I and II molecules to both CD8(+) and CD4(+) T cells, favoring a complete and coordinated immune response.

Cited by 38 publications

References 41 publications

Optimization of protein loaded PLGA nanoparticle manufacturing parameters following a quality-by-design approach

Optimization of protein loaded PLGA nanoparticle manufacturing parameters following a quality-by-design approach

In vitro evaluations on canine monocyte-derived dendritic cells of a nanoparticles delivery system for vaccine antigen against Echinococcus granulosus

Polymer-Based DNA Delivery Systems for Cancer Immunotherapy

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