Marie Curie Intra European Fellowship (IEF)
Phenylketonuria (PKU) is the most common genetic enzyme defect, with an overall incidence in Europe and the USA of 1:10,000-20,000 live births per year. Patients suffer from a genetic defect in the liver enzyme phenylalanine hydroxylase (PAH), which normally metabolizes the amino acid phenylalanine (Phe) into the amino acid tyrosine. This specific enzyme defect, which results in an increase in the level of systemic Phe in the first few years of life, can lead to severe mental retardation. The implementation of newborn screening to detect PKU has facilitated the early use of dietary treatment (i.e., reduced Phe uptake), however, this diet is difficult to follow and does not prevent elevation of blood Phe during episodes of fever and infection. Furthermore, dietary treatment is difficult to maintain during pregnancy as both an elevated Phe blood level as well as a low Phe diet is associated with an increased frequency in birth defects.
i) Assembly and characterization of PDA-based capsosomes
The design of compartmentalized carriers as artificial cells is envisioned to be an efficient tool with potential applications in the biomedical field. The advent of this area has witnessed the assembly of functional, bio-inspired systems attempting to tackle challenges in cell mimicry by encapsulating multiple compartments and performing controlled encapsulated enzymatic catalysis. Although capsosomes, which consist of liposomes embedded within a polymeric carrier capsule, are among the most advanced systems, they are still amazingly simple in their functionality and cumbersome in their assembly. We reported on capsosomes by embedding liposomes within a PDA carrier shell created in a solution-based single-step procedure. We demonstrated for the first time the potential of PDA-based capsosomes to act as artificial cell mimics by performing a two-enzyme coupled reaction in parallel with a single-enzyme conversion by encapsulating three different enzymes into separated liposomal compartments. In the former case, the enzyme uricase converts uric acid into hydrogen peroxide, CO2 and allantoin, followed by the reaction of hydrogen peroxide with the reagent Amplex Ultra Red in the presence of the enzyme horseradish peroxidase to generate the fluorescent product resorufin. The parallel enzymatic catalysis employs the enzyme ascorbate oxidase to convert ascorbic acid into 2-L-dehydroascorbic acid.
The publication on this aspect can be found here.
Recent Progress of Liposomes in Nanomedicine, Leticia Hosta-Rigau, Philipp Schattling, Boon M. Teo, Martin Lynge, Brigitte Städler*, J. MATER. CHEM. B, 2014 just accepted
Confined Multiple Enzymatic (Cascade) Reactions within Poly(dopamine)-based Capsosomes, Leticia Hosta-Rigau, Maria J. York-Duran, Yan Zhang, Kenneth N Goldie, Brigitte Städler*, ACS APPL. MATER. INTERFACES 2014 just accepted
Liposome-Containing Polymer Films and Colloidal Assemblies towards Biomedical Applications, Boon M. Teo, Leticia Hosta-Rigau, Martin E. Lynge, Brigitte Städler*, NANOSCALE 2014 6, 6426-6433
Selected Topics in Nanomedicine, (World Scientific), Editor: Thomas Ming Swi Chang, Chapter 12: Subcompartmentalized Systems Towards Therapeutic Cell Mimicry. Leticia Hosta-Rigau, Brigitte Städler*
Cholesterol – A Biological Compound as Building Block in Bionanotechnology, Leticia Hosta-Rigau, Yan Zhang, Boon M. Teo, Almar Postma, Brigitte Städler*, NANOSCALE, 2013, 5, 89-109