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