BIO- AND NANOTECHNOLOGY APPROACHES TO DRUG DELIVERY
Prof. dr. Enrico Mastrobattista
In this research program biotechnology is applied to produce lipid and protein-based drug delivery systems at the nano-scale. These bio-inspired drug delivery systems can consist of recombinant (poly)peptides that self-assemble into well-defined supramolecular structures, such as micelles, vesicles, or nanotubes or that can specifically interact with DNA to form condensed nanospheres. In addition, synthetic biological systems such as artificial microbes and viruses are being developed for vaccination and gene delivery purposes.
Recombinant and Semi-Synthetic Drug Delivery Systems
This sub-project deals with the recombinant production of de novo proteins that can be used as building blocks to construct protein- or semi-synthetic drug delivery systems. Building blocks include amphiphilic peptides that can self-assemble into nanospheres and recombinant protein polymers containing nonnatural amino acids to generate hybrid materials. Application of these bio-inspired drug delivery systems include photodynamic therapy and in situ triggered release systems.
Artificial Microbes for Vaccination
Using cell-free protein synthesis inside liposomal compartments our aim is to design artificial microbes for vaccination purposes. So far, we have demonstrated that cell-free synthesis of a model antigen from a DNA template inside liposomes results in high serum IgG titers against the in situ produced antigen when liposomes were injected i.m. in mice. We are currently investigating whether such antigen-expressing immunostimulatory liposomes (AnExILs) can also induce cellular immune responses.
Biomimetic Vectors for Gene Delivery
In this sub-project, an attempt is being made to close the gap between viral and synthetic vectors for gene delivery in terms of efficiency and safety by combining synthetic and biological components into a single gene delivery system. Both rational and high-throughput approaches will be followed to optimize and test these biomimetic vectors for their gene transducing capacity in vitro and in vivo.
Increasing the Cost-Effectiveness of Biopharmaceuticals
Biopharmaceuticals (i.e. protein and nucleic acid-based drugs) are often rather expensive and as a consequence, not all patients in need of these medicines can be treated. To increase the accessibility of this important class of medicines for patients in need we work on methods to either decrease production costs or, by applying drug delivery approaches, to increase the efficacy of existing biopharmaceuticals.
- Jerry Lau, Vaccine Delivery Systems based on Self-Assembling Peptides
- Charis Rousou, Ultrasound-mediated drug delivery to the retina
- Johanna Walther, Design of lipid nanoparticles for direct in vivo gene editing
- Danny Wilbie, Intracellular kinetics of CRISPR-Cas components
- Mert Öktem, Cell penetrating peptides for ex vivo gene editing
- Roderick van den Berg, Stability of mAb therapeutic products
- Albert van Hell. Structural and functional characterization of self-assembling amphiphilic oligopeptides. ISBN 978-90-393-4986-1. 2009
- Niels Hagenaars. Towards an intranasal influenza vaccine based on whole inactivated influenza virus with N,N,N-trimethyl chitosan as adjuvant. ISBN 978-94-90588-01-4. 2009
- Ethlinn van Gaal. DNA-transporting nanoparticles : design and in vitro evaluation of DNA and formulation for non-viral gene delivery. ISBN 978-90-3935411-7. 2010
- Inge van Rooy. Targeted liposomes for drug delivery across the blood-brain barrier. ISBN 978-90-393-5522-0. 2011
- Albert de Graaf. Self-assembled materials from thermosensitive and biohybrid block copolymers. ISBN 978-90-393-5753-8. 2012
- Markus de Raad. Design and recombinant production of combinatorial peptide libraries for gene delivery. ISBN 978-90-393-6059-0. 2013
- Negar Babae. Discovery and delivery of anti-angiogenic miRNAs for cancer treatment. ISBN 978-90-393-60460. 2013
- Afrouz Yousefi. Nanocarriers for systemic siRNA delivery to tumor vasculature. ISBN 978-90-393-6106-6. 2014
- Erik Teunissen. Towards the directed evolution of virus-like particles derived from polyomaviruses. ISBN 978-90-393-6167-2. 2014
- Luis Novo. Decationized polyplexes for targeted delivery of nucleic acids: from carrier design to in vivo evaluation. ISBN 978-90-393-6220-4. 2014
- Mazda Rad-Malekshahi. Self-assembled peptide nanostructures: production, structural characterization and in vivo application as cancer vaccine. ISBN:978-90-393-6395-9. 2015
- Erik Oude Blenke. Intracellular delivery of RNA therapeutics with lipid nanoparticles. ISBN: 978-94-6295-582-0. 2017
- Bo Lou. Multifunctional polymeric nanoparticles for RNA delivery : from carrier design to cancer immunotherapy. ISBN: 978-90-393-7034-6. 2018
- Mohammed Al-Dosari. Accessibility and Availability of Orphan Drugs: Challenges and Potential Solutions. ISBN: 978-94-6375-116-2. 2019.
List of key publications
- Oude Blenke, E., van den Dikkenberg, J., van Kolck, B., Kros, A., & Mastrobattista, E. (2016). Coiled coil interactions for the targeting of liposomes for nucleic acid delivery. Nanoscale, 8(16), 8955-8965.
- Rad-Malekshahi, M., Visscher, K. M., Rodrigues, J. P., De Vries, R., Hennink, W. E., Baldus, M., ... & Weingarth, M. (2015). The supramolecular organization of a peptide-based nanocarrier at high molecular detail. Journal of the American Chemical Society, 137(24), 7775-7784.
- Oude Blenke, E., Klaasse, G., Merten, H., Plückthun, A., Mastrobattista, E., & Martin, N. I. (2015). Liposome functionalization with copper-free “click chemistry”. Journal of Controlled Release, 202, 14-20.
- Mastrobattista, E. & Hennink, W. E. Polymers for gene delivery: Charged for success. Nature Materials 11, 10–2 (2012).
- Mastrobattista, E., Van Der Aa, M. A., Hennink, W. E., & Crommelin, D. J. (2006). Artificial viruses: a nanotechnological approach to gene delivery. Nature reviews Drug discovery, 5(2), 115-121.