Leiden University has developed a radically different method for large scale production of diverse nanoparticles and their alloys.

Gold nanoparticles show surprisingly strong interactions with light in the visible range, which can be divided into scattering, absorption, and photoluminescence.

Artificial photosynthesis aims to produce fuels from solar energy using chemical processes. In semi-artificial photosynthesis, a hybrid approach is taken using both chemical and biotechnology approaches. We aim to develop hybrid systems between light-harvesting nanoparticles and redox-enzymes (oxidoreductases)…

In this work, we investigate the minute circular dichroism effects of single nanoparticles.To this aim, we apply photothermal imaging with a polarization-modulated heating beam.

Metal-based prodrugs based on ruthenium(II) polypyridyl complexes have proven to be very suitable for application in both photodynamic therapy (PDT) and photo-activated chemotherapy (PACT).

Promotores: Prof.dr. W.J.G.M. Peijnenburg & Dr. M.G. Vijver

Despite the fact that gold nanoparticles (GNPs) are one of the most studied nanoparticles, there is still a necessity for new approaches allowing for effective protective coating to enable wider use of GNPs in biomedical applications.

The work described in this dissertation contributes to a better mechanistic understanding of nanoparticles in vivo. To achieve that goal, we used the zebrafish as a highly predictive pre-screening model of nanoparticles.

A very large part of intravenously administered nanoparticles are cleared through the liver. Within the liver, most nanoparticles are thought to be sequestered by macrophages (Kupffer cells). To achieve effective cell-specific targeting of drugs and non-viral gene delivery vectors, improved mechanistic…

What is the mechanism of action preceding a physiological effects induced by metallic nanoparticles?

This thesis aimed to investigate the impact of exposure dynamics, relative contributions of ENPs(particle) and ENPs(ion), and dosing regimens on the toxicity of ENPs varying in different physico-chemical properties, on the composition and functioning of soil microbial communities.

There is concern about the threat that nanoplastics (NPs) may pose to both wildlife and humans. This thesis explores the mechanisms of toxicity of polystyrene nanoparticles (PS-NPs) in chicken embryo.

Bet v1, the major allergen in birch pollen, is one of the main causes of allergies such as asthma and rhino-conjunctivitis. Additionally it is the main cause of birch pollen allergy in humans.

Fate and toxicity of copper nanoparticles was related to the water chemistry of the environment and pristine size.

The findings in this thesis improve the understanding of 1) the relationship between exposure characteristics and toxicity of ENPs, 2) the joint toxic action of ENP mixtures and the comparison to metal salt mixtures, 3) how NOM affects the individual and joint toxicity of ENPs, 4) the extent of trophic…

This thesis focuses on the application of lipid-based nanomedicine in drug delivery, including small molecular antitumor drugs and biomacromolecules including mRNA, and evaluates their biological performance.

The aim is to discover where differently shaped metal nanoparticles distributes in Danio rerio, linking the distribution with genomic responses and so come up with a Mode of Action.

Promotor: M.A.G.J. Orrit

This thesis describes a study from both a theoreticaL and an experimental point of view.

Promotores: Prof.dr. W.J.G.M. Peijnenburg & Dr. M.G. Vijver

1. To what extent do metallic NPs added to soil extractions change the activity, abundance, or community composition of microbes? 2. How do the effects of metallic NPs on soil microbes differ from the effects of the ions shedding from corresponding NPs?

Promotor: Prof.dr. J.W.M. Frenken

Promotor: A. Kros

Promotores: Prof.dr. W.J.G.M. Peijnenburg & Dr. M.G. Vijver

Promotor: A. Kros, Co-promotor: R.R.C.L. Olsthoorn

Exploring the mechanism of targeted nanoparticle-mediated drug delivery using the zebrafish model

This doctoral thesis is an effort to understand how lipid phase-separation induced by diacylglycerol analogues in lipid-based nanoparticles affects their in vivo behavior, leading to specific nanoparticle-protein communications and selective cell targeting.

Cationic peptide amphiphile nanoparticles are employed for co-delivery of immune modulator CpG and antigen. This results in better targeting to the antigen presenting cells and eliciting strong Th1 response, which is effective against the intracellular pathogens.

Novel entities may pose risks to humans and the environment. The small particle size and relatively large surface area of micro- and nanoparticles (MNPs) make them capable of adsorbing other novel entities, leading to the formation of aggregated contamination.

Promotor: J.M. van Ruitenbeek, Co-Promotor: S.J. van der Molen

Dendritic cells (DC) play a prominent role in the priming of CD8(+) T cells. Vaccination is a promising treatment to boost tumor-specific CD8(+) T cells which is crucially dependent on adequate delivery of the vaccine to DC.

SMR can be used to measure the mass of adsorbed protein to nanoparticles with a high precision in the presence of free protein.

The purpose of this study was to investigate the formation and growth kinetics of complexes between proteins and oppositely charged polyelectrolytes.

Tuberculosis (TB) is a major global health problem caused by the bacterium Mycobacterium tuberculosis (Mtb). In 2015, there were estimated to be 10.4 million new cases and 1.8 million deaths ascribed to TB, making it one of the top 10 causes of death worldwide. Unfortunately, the only current registered…

Describe and identify what dosimetry parameters are of importance to interpret dose-response relationships (eg., mortality, sub-lethal, growth or reproduction inhabitation, DNA damage and reactive oxygen species, etc. ) for metal-based nanoparticles? How to develop quantitative models that enable to…

Mycobacterium tuberculosis (Mtb), the pathogen causing tuberculosis (TB), is the leader among all pathogens responsible for the most human deaths today and it is considered as one of the top 10 causes of death worldwide. There is an increasing occurrence of multidrug-resistant and even totally drug-resistant…

Leiden PhD student Xuequan Zhou has designed a new promising molecule that efficiently kills cancer cells, but does not harm healthy tissue. The trick: the drug is only active when irradiated with light. Zhou’s new compound does this extra efficiently by cleverly self-organising into nanoparticles.…

Gold nanorods are biocompatible nanoparticles that present an excellent two-photon signal that can be used to get high spatial resolution inside living cells. Gold nanorods are photostable and therefore can be followed inside cells for long time, with possible applications as trackers in live cells.

'Quality Nano' funded research of the Institute of Environmental Sciences to work in Exeter University for 20 working days, which allows the institute to access highly advanced equipment needed for evaluation the toxicity of nanoparticles.

It's pretty hard to spot a single 5 nanometer particle. Leiden physicists pulled it off by turning a 120 nm gold rod into a detector.

Tiny selenium particles could have a therapeutic effect on ischemic brain strokes by promoting the recovery of brain damage. Pharmacologists, including Alireza Mashaghi from the Leiden Academic Centre for Drug Research discovered that selenium nanoparticles inhibit molecular mechanisms that are responsible…

If it’s up to PhD student Guangsheng Du, patients don’t need to worry about big needles anymore. At the Leiden Academic Center for Drug Research (LACDR), he studied the use of microneedles and nanoparticles as a new vaccination system. ‘I want to create a more patient-friendly delivery method.’ He defends…

Chemotherapy that does not harm the body, but effectively fights cancer cells: that is the goal of chemist Sylvestre Bonnet and his team. During his PhD research, chemist Xuequan Zhou brought that goal a little closer. He developed molecules that, upon injection in the bloodstream, self-assemble into…

Assessing the risks of engineered nanomaterials (ENMs) solely on the basis of experimental assays is time-consuming, resource intensive, and constrained by ethical considerations (such as the principles of the 3Rs of animal testing). The adoption of computational toxicology in this field is a high p…

Although nanoparticles are extensively used in various applications like consumer products and have most probably entered the environment, little is known about the effects of these particles on living organisms.

In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses.

How to make a quantitative assessment of the relative contribution to toxicity of ions and particles? Is the toxicity of nanoparticles related to their size or shape? Which physicochemical property of nanoparticles is an appropriate dose metric of nanoparticles?

The external tissues of plants and animals are colonized by microbial communities termed microbiota. When organisms are exposed to environmental pollutants, these substances will therefore encounter microbiota at the exposure interface.

Currently, several successful vaccines are available. However, for pathogens with a highly variable genetic composition, and for which serum IgG antibodies are not a useful correlate of protection, effective vaccines are yet to be developed.