Growth and development affect the metabolism of drugs administered to neonates, infants, and children.

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

This thesis investigates the relations between metabolism and anatomy through the use of Magnetic Resonance Imaging (MRI).

PhD defence

This thesis advances our understanding of lipid uptake, a vital first step in lipid metabolism, by developing innovative click chemistry-based tools to study how immune cells internalize lipids.

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…

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.

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.

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…

'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.

This thesis describes biochemical investigations of glucocerebrosidase (GBA), the lysosomal β- glucosidase that is deficient in Gaucher disease (GD).

Advanced UHF MRI techniques provide powerful tools for studying the zebrafish brain, an emerging model in neurological research. In this work, various MRI and localized MRS methods are optimized and employed for UHF strength for studying the zebrafish brain.

Our research aims to develop drugs that boost the host immune response to better defend us against mycobacteria.

Streptomyces are prolific producers of enzymes and secondary metabolites, including more than 50% of all clinical antibiotics. This makes them highly attractive for medical, biotechnological, and industrial purposes.

Parkinson's disease is the second most common neurodegenerative disease in the world. One of its symptoms is the loss of dopaminergic neurons in the substantia nigra pars compacta.

How can we develop new chemical biology tools and approaches to understand and interfere with glucosylceramide metabolism in relation to Gaucher disease?

PhD defence

Clearance is the most important pharmacokinetic parameter for drug dose selection. Pharmacokinetic information is typically first available in the adult population, and in general only limited pharmacokinetic data are available in children when drugs enter into the market. It is therefore of the utmost…

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.

With an emphasis on developing novel miktoarm star polymers termed PeptoMiktoStars, this thesis leverages asymmetric polymeric polypept(o)ide frameworks to advance their effectiveness in delivering hydrophobic drugs and nucleic acids.

Quantifying physical activity (using accelerometers) and combining the frequency and intensity of activities with health data (brain MRI, traditional clinical parameters and metabolomics) is of utmost importance to monitor mobility and health among older individuals and study health promotion during…

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.…

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

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.

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.

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…

Leiden biotech startup Azafaros has successfully completed a funding round, raising 25 million euros of investments for developing treatments of rare metabolic disorders. The company holds exclusive license to a library of novel patented compounds discovered by experts from Leiden University.

The work in this thesis describes the fundamental role of Lkb1 as a conductor of metabolism-related processes in zebrafish larvae.

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.

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…

Nicotinamide adenine dinucleotide (NAD+) is the substrate used for the introduction of the ubiquitous and highly dynamic PTM in which either one or multiple adenosine diphosphate ribose (ADPr) moieties are covalently attached to a nucleophilic side chain of an specific amino acid in the target protein…

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…

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…

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…

Can bacteria be engineered to convert methanol into valuable chemicals with high efficiency?

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.

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.

This thesis focuses on the synthesis, characterization and performance towards CO2 electroreduction of mono and bi-metallic particles based on p-block metals

Bacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments.

Promotor: Prof.dr. W. Jiskoot, Co-promotor: A. Kros

Can Cyanobacteria be engineered to convert the greenhouse gas carbon dioxide into the valuable chemical isoprene?

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.

Particles are omnipresent in biopharmaceutical products. In protein-based therapeutics such particles are generally associated with impurities, either derived from the drug product itself (e.g. protein aggregates), or from extrinsic contaminations (e.g. cellulose fibers).

Ferritin is a spherical metalloprotein, capable of storing and releasing iron in a controllable way. It is composed of a protein shell of about 12 nm and within its cavity, iron is stored in a mineral form.