The Waterloo Institute for Nanotechnology (WIN) is pleased to present a Distinguished Lecture by Jan van Hest, Professor of Bio-organic Chemistry at Eindhoven University of Technology!
Registration is required. Please register early as there is limited seating. Coffee & Timbits will be provided!
Employing stimulus-responsive nanoparticles for photodynamic therapy
Abstract
Photodynamic therapy (PDT) is a highly interesting approach to treat cancer. It is based on the excitation of a photosensitizer using (NIR) light; energy from the excited state is subsequently translated to oxygen to create singlet oxygen species. For the success of this treatment, the photosensitizer has to be positioned at the tumour site and should deeply penetrate this tissue,
In this contribution, we report on several novel approaches to achieve effective PDT. In our first approach, we employ porphyrin-dipeptide conjugates, which are modified with poly(ethylene glycol) chains for solubility, and in which the porphyrin is employed as a photosensitizer. These conjugates assemble into nanofibers at physiological pH. At decreased pH values found in tumour tissue, the fibres start to aggregate. Based on this effect, the photosensitizer accumulates in the tumour tissue, and PDT can be effectively executed. Since the porphyrin conjugate is also fluorescent, the accumulation of the fibres and the efficacy of PDT can be conveniently followed with fluorescence.
In another approach, we aim to achieve a deeper tumour penetration of our photosensitizer to ensure that PDT is not restricted to the periphery of the tumour. For this purpose we have developed size-switchable nanoparticles based on elastin-like polypeptides (ELPs). ELPs display a lower critical solution temperature behavior determined by the amino acid composition. Using protein engineering, diblock ELPs can be made that form micelles. The micelles are furthermore modified with tumour-targeting antibodies, photosensitive amino acids and a photosensitizer. Due to the design, the ELPs are changed into more hydrophilic building blocks upon light irradiation, which leads to their rearrangement into targeted PDT nanoclusters with higher penetration strength and PDT efficacy.
Finally, we employ polymeric vesicles which are functionalized with aggregation-induced emission (AIE) units. These units not only lead to intrinsic fluorescence of the particles, but also to effective PDT. In order to improve therapeutic efficacy, the polymersomes have been equipped with a motile function, which leads to enhanced penetration and cell killing.
Biography
Jan van Hest obtained his PhD in macro-organic chemistry with professor Bert Meijer from Eindhoven University of Technology (TU/e) in 1996. He then worked as a postdoc researcher on protein engineering with professor David A. Tirrell at the University of Massachusetts. In 1997 van Hest started working at DSM (Geleen), first as a researcher and later as group head in the development of new material concepts. In 2000 Van Hest was appointed as full professor at Radboud University Nijmegen. As of September 2016, he holds the chair of Bio-organic Chemistry at TU/e. Over 30 PhD candidates have gained their doctorates under his supervision. He has published over 300 scientific articles (H-index 57) and is (co-)inventor of 17 patents and patent applications. Jan van Hest is also the joint founder of the start-ups Encapson, FutureChemistry, Noviosense and Noviotech