Single-Chain Polymer Nanoparticles in Controlled Drug Delivery
Naomi Hamelmann is a PhD student in the research group Biomolecular Nanotechnology. Supervisors are dr.ir. J.M.J. Paulusse and prof.dr. J.J.L.M. Cornelissen from the Faculty of Science & Technology.
Controlled drug delivery aims to transport therapeutics to specific regions in the human body, and nanoparticles (NPs) have proven particularly effective in increasing local drug concentrations, protecting unwanted degradation of therapeutics and diminishing side effects. Polymeric nanoparticles provide the ability to adapt their size, composition and functionalization, making use of the enormous synthetic toolbox developed over the past decades.
In this thesis, Single-Chain Polymer Nanoparticles (SCNPs) were synthesized based on intramolecular crosslinking forming particles of around 10 nm in diameter. The size of SCNPs is in the same size regime as proteins and therefore SCNPs are an interesting nanoparticle class for biomedical applications. In Chapter 3 SCNPs for controlled drug delivery in the application of targeting the malaria parasite in mosquitos was investigated. The focus of this thesis was further on the cytosolic delivery of SCNPs to facilitate controlled drug delivery. The intracellular delivery of SCNPs was investigated via vector based delivery using polyplex formation of negatively charged SCNPs and positive polymers (Chapter 4), and via surface functionalization of SCNPs with tertiary amines (Chapter 5 and 6). The successful cytosolic delivery was demonstrated by confocal laser scanning microscopy in endothelial and HeLa cells. Conjugation of therapeutics, including doxorubicin and atovaquone was investigated for the application against cancer (Chapter 4 and 6). We have illustrated in this work that efficient nanocarriers for controlled drug delivery can be achieved by controlling the intracellular fate of SCNPs.