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Understanding the interaction of nanoparticles with B lymphocytes in vitro and in vivo

English title Understanding the interaction of nanoparticles with B lymphocytes in vitro and in vivo
Applicant Bourquin Carole
Number 156871
Funding scheme Project funding (Div. I-III)
Research institution Département de Médecine Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Immunology, Immunopathology
Start/End 01.02.2015 - 31.12.2018
Approved amount 397'000.00
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All Disciplines (3)

Discipline
Immunology, Immunopathology
Molecular Biology
Biochemistry

Keywords (12)

Human Health; Immunology; Toxicology; Antibody; In vitro systems; Antigen; In vivo systems; B Lymphocytes; Nanoparticles; Nanomedicine; Nanotoxicology; Theranostics

Lay Summary (German)

Lead
Understanding the interaction of nanoparticles with B lymphocytes in vitro and in vivo SNSF Division III Project PI: Dr. Martin J.D. Clift, BioNanomaterials, Adolphe Merkle Institute, University of FribourgCo-App: Prof. Dr. Carole Bourquin, Chair of Pharmacology, University of Fribourg
Lay summary

Nanopartikel (NPs), d.h. Materialien, deren drei Dimensionen im Nanobereich (1-100nm) liegen, werden spezifisch für eine Fülle von Anwendungen entwickelt, beispielsweise für Kosmetikprodukte, Sportausrüstung, Informationstechnologie und die Medizin. NPs sind hierfür sehr attraktiv aufgrund der unlimitierten Möglichkeiten, ihre spezifischen physiko-chemischen Charakteristika zu manipulieren (z.B. Grösse, Oberflächenladung, Form) und so die Ausprägung von neuartigen Eigenschaften zu ermöglichen. Trotz der möglichen Vorteile ist eine klare Vorstellung des Einflusses von NPs und deren physischer Eigenschaften auf die menschliche Gesundheit bisher begrenzt. Nichtsdestotrotz sind NPs vielversprechende Kandidaten für Systeme zur Verabreichung von Impfstoffen, um eine schützende Immunantwort zu induzieren. Tatsächlich ist es möglich, ein und dasselbe NP mit den zwei essentiellen Komponenten einer Impfung, ein Adjuvanz und das Antigen, zu beladen. Ungeachtet dessen ist das Wissen um die Fähigkeit von NPs mit dem menschlichen Immunsystem zu interagieren und die daraus resultierenden Auswirkungen eines der am wenigsten untersuchten Felder der NP-Toxikologie. Speziell B-Lymphozyten stellen einen entscheidenden Zelltyp für die Entwicklung einer Antikörper-vermittelten Immunantwort auf eine Impfung dar. Im Hinblick auf das therapeutische Potential von NPs (z.B. Schutzimpfungen) ist es notwendig, den direkten Einfluss zu charakterisieren, den NPs möglicherweise auf B-Zellen haben. Das Ziel dieses Forschungsprojekts ist es deshalb mit Hilfe einer Reihe von gut charakterisierten NPs, die NP-Interaktion und den biologischen Einfluss auf B-Lymphozyten einzuschätzen und ausserdem zu untersuchen, wie die verschiedenen NPs die Funktion von B-Lymphozyten beeinflussen können. Die Umsetzung der Forschungsziele werden wichtige Einblicke in die Anwendbarkeit von NPs in der Medizin liefern und das Verständnis über die möglichen Gefahren auf die menschliche Gesundheit erweitern.

 

Direct link to Lay Summary Last update: 25.02.2015

Lay Summary (English)

Lead
Understanding the interaction of nanoparticles with B lymphocytes in vitro and in vivo SNSF Division III Project PI: Dr. Martin J.D. Clift, BioNanomaterials, Adolphe Merkle Institute, University of FribourgCo-App: Prof. Dr. Carole Bourquin, Chair of Pharmacology, University of Fribourg
Lay summary

Nanoparticles (NPs), defined as materials thathave all three dimensions in the nanoscale (1-100nm), are being specifically engineered for use in a plethora of Their applications: such as cosmetics, sports equipment, information technology and medicine. NPs are highly attractive in this regard due to the endless possibilities to manipulate specific physical Their Characteristics ( eg size, surface charge, shape) did enable them to exhibit novel properties. Despite potential advantages Opinion thesis, clear understanding of the impact of NPs and Their physical properties, upon human health remains limited. Nonetheless, NPs have been Proposed as promising delivery systems for vaccinations in order to induce protective immune responses. Indeed, it is Possible to load Onto the same NP the two essential components of a vaccine antigen in adjuvant and on. Despite this, knowledge as to the ability for NPs to interact with, and Their impact upon the human immune system is one of the least Studied areas as regards NP toxicology. B lymphocytes, in particularmente, represent a Crucial cell type for the development of antibody responses to vaccination. Considering the therapeutic potential of NPs ( eg for vaccination), it is essential to characterize the direct impact did NPs May have on the function of B lymphocytes. THEREFORE the purpose of this research project is, using a well-Characterised panel of NPs, to assess the NP interaction and biological impact upon B lymphocytes, as well as to investigate how the different NPs May influence the function of B lymphocytes. Realization of the objectives of this research will Provide Important insight towards the Applicability of NPs as medical applications, as well as understanding Their potential hazard towards human health.

Direct link to Lay Summary Last update: 25.02.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation
Mottas Inès, Bekdemir Ahmet, Cereghetti Alessandra, Spagnuolo Lorenzo, Yang Yu-Sang Sabrina, Müller Marie, Irvine Darrell J., Stellacci Francesco, Bourquin Carole (2019), Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation, in Biomaterials, 190-191, 111-120.
Engineered hybrid spider silk particles as delivery system for peptide vaccines
Lucke Matthias, Mottas Inès, Herbst Tina, Hotz Christian, Römer Lin, Schierling Martina, Herold Heike M., Slotta Ute, Spinetti Thibaud, Scheibel Thomas, Winter Gerhard, Bourquin Carole, Engert Julia (2018), Engineered hybrid spider silk particles as delivery system for peptide vaccines, in Biomaterials, 172, 105-115.
NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I interferon response
Oberson Anne, Spagnuolo Lorenzo, Puddinu Viola, Barchet Winfried, Rittner Karola, Bourquin Carole (2018), NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I interferon response, in Oncotarget, 9(5), 5641-5651.
Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node for immunostimulation
Widmer Jérôme, Thauvin Cédric, Mottas Inès, Nguyen Van Nga, Delie Florence, Allémann Eric, Bourquin Carole (2018), Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node for immunostimulation, in International Journal of Pharmaceutics, 535(1-2), 444-451.
A novel technique to determine the cell type specific response within an in vitro co-culture model via multi-colour flow cytometry
Clift Martin J. D., Fytianos Kleanthis, Vanhecke Dimitri, Hočevar Sandra, Petri-Fink Alke, Rothen-Rutishauser Barbara (2017), A novel technique to determine the cell type specific response within an in vitro co-culture model via multi-colour flow cytometry, in Scientific Reports, 7(1), 434-434.
A rapid screening method to evaluate the impact of nanoparticles on macrophages
Mottas Inès, Milosevic Ana, Petri-Fink Alke, Rothen-Rutishauser Barbara, Bourquin Carole (2017), A rapid screening method to evaluate the impact of nanoparticles on macrophages, in Nanoscale, 9(7), 2492-2504.
Antimicrobial silver-filled silica nanorattles with low immunotoxicity in dendritic cells
Priebe Magdalena, Widmer Jérôme, Suhartha Löwa Nina, Abram Sarah-Luise, Mottas Inès, Woischnig Anne-Kathrin, Brunetto Priscilla S., Khanna Nina, Bourquin Carole, Fromm Katharina M. (2017), Antimicrobial silver-filled silica nanorattles with low immunotoxicity in dendritic cells, in Nanomedicine: Nanotechnology, Biology and Medicine, 13(1), 11-22.
A biological perspective towards the interaction of theranostic nanoparticles with the bloodstream - what needs to be considered?
Clift Martin James David, Dechezelles Jean-Francois, Rothen-Rutishauser Barbara, Petri-Fink Alke (2015), A biological perspective towards the interaction of theranostic nanoparticles with the bloodstream - what needs to be considered?, in Frontiers in Chemistry, 3, 7.

Collaboration

Group / person Country
Types of collaboration
NCCR Bio-inspired materials Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Thomas Bein, University of Munich Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
NanoInterCell Research Group/EMPA St. Gallen Switzerland (Europe)
- Research Infrastructure
Prof. Eric Allémann, Université de Genève Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
BIC – the Bern Immunology Club Talk given at a conference “HMGB1: Controlling B-cell trafficking in the Peyer’s patches” 26.09.2018 Bern, Switzerland Bourquin Carole;
NanoTox 2018 Poster “Determining the impact of gold nanoparticle shape and surface on B lymphocyte function in vitro and in vivo” 18.09.2018 Neuss, Germany Bourquin Carole; Hocevar Sandra;
6th Cell Migration Retreat Talk given at a conference . “How gold nanoparticles effect B lymphocytes and their function ?” 05.09.2018 Gerzensee, Switzerland Bourquin Carole; Hocevar Sandra;
6th Cell Migration Retreat Talk given at a conference “A new role for HMGB1” 05.09.2018 Gerzensee, Switzerland Hocevar Sandra; Bourquin Carole;
32nd Seminar in Pharmaceutical Sciences, From an idea to the patient Talk given at a conference “Fighting cancer with spider silk” 27.08.2018 Zermatt, Switzerland Bourquin Carole; Hocevar Sandra;
32nd Seminar in Pharmaceutical Sciences, From an idea to the patient Talk given at a conference “Gold nanoparticles and their effect on B lymphocyte function” 27.08.2018 Zermatt, Switzerland Bourquin Carole; Hocevar Sandra;
European Congress on Biotechnology (ECB 2018) Talk given at a conference “How not to prepare your CV” 03.07.2018 Geneva, Switzerland Bourquin Carole;
27th Immunology Day Talk given at a conference “A new role for HMGB1: Controlling B-cell trafficking in the Peyer’s patches” 20.06.2018 Geneva, Switzerland Bourquin Carole; Hocevar Sandra;
1st Symposium of the Centre for Translational Research in Oncohaematology, Campus Biotech Talk given at a conference “The Immunopharmacology of cancer” 18.06.2018 Geneva, Switzerland Hocevar Sandra; Bourquin Carole;
5th ProDoc Cell Migration retreat Talk given at a conference “Effects of gold nanoparticles on B cells” 22.09.2017 Bellinzona, Switzerland Bourquin Carole; Hocevar Sandra;
31st Seminar in Pharmaceutical Sciences, PhD program in Pharmaceutical Sciences : Pharmacology from Bench to Bedside Talk given at a conference “How not to prepare your CV” 31.08.2017 Zermatt, Switzerland Bourquin Carole; Hocevar Sandra;
31st Seminar in Pharmaceutical Sciences: Pharmacology from Bench to Bedside Poster “Polymer-coated gold nanoparticles do not alter the activation status or (pro-)inflammatory response of human B lymphocytes in vitro” 28.08.2017 Zermatt, Switzerland Hocevar Sandra; Bourquin Carole;
31st Seminar in Pharmaceutical Sciences; Pharmacology from Bench to Bedside Talk given at a conference “Interaction of gold nanoparticles with B lymphocytes” 28.08.2017 Zermatt, Switzerland Bourquin Carole; Hocevar Sandra;
Center for Translational Research in Onco-hematology, University of Geneva Individual talk “How to harness myeloid-derived suppressor cells” 18.05.2017 Geneva, Switzerland Bourquin Carole;
Collège des professeurs de la Faculté de Médecine, Université de Genève Individual talk “Comment prédire l’effet des nanoparticules sur notre système immunitaire ?” 09.05.2017 Geneva, Switzerland Bourquin Carole;
10 th European and Global Conference and Exhibition for Clinical Nanomedicine & Targeted Medicine: Witnessing the Solutions and Tackling the Hurdles Poster Polymer-coated gold nanoparticles do not alter the activation status or (pro-)inflammatory response of human B lymphocytes in vitro 07.05.2017 Basel, Switzerland Hocevar Sandra; Bourquin Carole;
Immunology Club Individual talk “Innate immune activation for cancer therapy” 31.03.2017 Geneva, Switzerland Bourquin Carole;
EPFL Individual talk “How to predict the impact of nanoparticles on the immune system” 15.03.2017 Lausanne, Switzerland Bourquin Carole;
Immunofest 2016 Talk given at a conference “Reprogramming innate immune signalling to improve cancer immunotherapy” 29.09.2016 Munich, Germany Bourquin Carole;
German Pharm-Tox Summit 2016 Talk given at a conference “Immunostimulation for cancer therapy: timing is everything” 29.02.2016 Berlin, Germany Bourquin Carole;


Self-organised

Title Date Place
6th Cell Migration Retreat 05.09.2018 Gerzensee, Switzerland
European Congress on Biotechnology (ECB 2018), Symposium 21 : Formulation, Package and Delivery 01.07.2018 Geneva, Switzerland
1st symposium of the Center for Research in Translational Onco-Hematology 18.06.2018 Genea, Switzerland
Life Sciences Switzerland (LS2) Annual Meeting 2018: Symposium de la Société Suisse de Pharmacologie Expérimentale 12.02.2018 Lausanne, Switzerland
31st Seminar in Pharmaceutical Sciences; Pharmacology from Bench to Bedside 28.08.2017 Zermatt, Switzerland

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Organisation d'un atelier pratique pour classes d'école primaire "Développons un médicament contre le cancer" Workshop 20.04.2018 Geneva, Switzerland Bourquin Carole;
Les jeudis de la Faculté de Médecine, Cycle Leçons inaugurales Talk 30.03.2017 Geneva, Switzerland Bourquin Carole;
Inauguration de l’EPGL : participation à la table ronde: "L’avenir des sciences pharmaceutiques fondamentales" Workshop 20.03.2017 Geneva, Switzerland Bourquin Carole;
Nano World Cancer Day 2017 Talk 20.02.2017 Geneva, Switzerland Bourquin Carole;
Journée portes ouvertes lors de l’inauguration des nouveaux locaux de l’EPGL Performances, exhibitions (e.g. for education institutions) 21.11.2016 Geneva, Switzerland Bourquin Carole;


Communication with the public

Communication Title Media Place Year
Media relations: radio, television "Des particules en soie d'araignée pour guérir le cancer" RTS, émission CQFD Western Switzerland 2018
Media relations: print media, online media "La soie d'araignée pour des vaccins d'un nouveau genre" Nombreux articles de presse Western Switzerland German-speaking Switzerland International 2018
Media relations: print media, online media Organisation d'un atelier pratique école primaire "Développons un médicament contre le cancer" PharmaJournal Western Switzerland 2018
Media relations: print media, online media "Narrowing the hunt for nanoparticles” NCCR Bio-Inspired Materials communication German-speaking Switzerland Western Switzerland 2017
Media relations: print media, online media "Une méthode révolutionnaire pour sélectionner les nanoparticules les plus prometteuses en médecine" Nombreux articles de presse Western Switzerland German-speaking Switzerland International 2017
Other activities “L’immunothérapie, une nouvelle stratégie contre le cancer” Western Switzerland 2017

Awards

Title Year
Best Poster Award : 500 EUR by the NanoImpact Journal 2018

Associated projects

Number Title Start Funding scheme
131264 Cellulose-based nanocomposite building materials: solutions and toxicity 01.05.2011 NRP 64 Opportunities and Risks of Nanomaterials
138284 Immunotherapy of gastric cancer: Enhancing T cell recruitment into tumors 01.01.2012 Project funding (Div. I-III)
141849 NCCR Bio-Inspired Materials: Center for Bio-Inspired Stimuli-Responsive Materials (phase I) 01.06.2014 National Centres of Competence in Research (NCCRs)
182317 HMGB1 and Gasdermin D: intratumoral targets to improve the response to cancer immunotherapy 01.01.2019 Project funding (Div. I-III)
138365 Realistic exposure scenarios to study nanoparticle-lung cell interactions 01.01.2012 Project funding (Div. I-III)

Abstract

It is widely accepted that exposure to engineered nanoparticles (NPs) can pose a considerable risk to human health when compared to their larger sized counterparts at the same mass dose. Despite this, their conceivable hazard is not fully understood. Independent of how NPs may enter the human body (i.e. inhalation, ingestion, injection or application via the epidermis), the manner in which the body will cope with a NP insult is similar; the immune system. The human immune system consists of both an innate and adaptive response, and is a complex physiological constitution of cells and molecules responsible for fighting infectious and non-infectious substances. Due to the inevitable use of engineered NPs in a variety of human-based medical applications (i.e. nanomedicine), in which NPs will be intentionally exposed to the human body via a variety of means for a theranostic approach, it is vital to determine how NPs interact with each component of the immune system to gain a thorough understanding of their potential advantages and disadvantages for biomedical applications. Despite this, the ability for NPs to interact with the human immune system is one of the least studied areas within the field of nanotoxicology. Of the limited research performed in regards to the hazard of NPs to the immune system, most has been with a focus upon how NPs interact with antigen presenting cells (APCs), specifically macrophages and dendritic cells. Additionally, in respect to the use of NPs within medical applications, NPs are intended to serve as carriers for proteins and other therapeutic molecules (i.e. vaccinations). In this sense, since NPs have been shown to interact with APCs (the critical cell type for the initiation of an immune response) they are proposed as advantageous delivery systems for vaccinations. Indeed, it is possible to load onto the same NP the two essential components of a vaccine, an antigen and an adjuvant. B lymphocytes represent a cell type that participates in both adaptive and innate immunity. B lymphocytes however, can also take up antigen and serve as antigen-presenting cells, thus affecting the critical initiation step in the induction of an immune response. Therefore, considering the high therapeutic potential of NPs for novel biomedical applications, in particular for the induction of protective antibody responses by vaccination, it is essential to characterize the direct impact that NPs may have on the dual function of B lymphocytes as APCs and antibody producers. Therefore the aim of this research project is to adopt a tiered approach using a well-characterised panel of NPs within specific biological fluid that (i) assesses the impact on (i.e. lethality and potential sub-lethal effects), and uptake mechanism(s)/intracellular localisation in B lymphocytes, as well as (ii) investigates how the different NPs may influence B lymphocyte maturation status and their potential to elicit an antibody response. To achieve these aims three clearly defined workpackages are proposed in which a variety of different physico-chemical NP types will be assessed via state-of-the-art microscopic and biochemical approaches. The aims of this research proposal identify an important knowledge gap within nanomedicine/nanotoxicology, specifically the impact of NPs upon B lymphocyte function. Through investigating the specific scientific questions detailed in the current proposal, important insight will be gained that will be essential towards the applicability of NPs within biomedical applications, as well as understanding their potential hazard towards human health.
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