Sabrina Oliveira was introduced to Utrecht University through an internship at the department of Pharmaceutical Sciences (2004) during her studies at the Faculty of Pharmacy of Coimbra University in Portugal. After graduation, she obtained an individual doctoral grant from the Portuguese Foundation for Science and Technology (FCT) to return to this department to do her PhD research on Targeted Cancer Therapies (2004-2008). She then worked as a postdoc on the development of tracers based on nanobodies for optical molecular imaging, in the group of Cell Biology, department of Biology (2008-2010) and the department of Pathology from the University Medical Center Utrecht (2010-2012). In 2012, she was awarded a VENI grant from the Netherlands Organisation for Research (NWO-STW), giving her the opportunity to start her own research line, which focuses on rendering photodynamic therapy more selective to cancer cells by using nanobodies. In 2016, she has received a Starting Grant from the European Research Council (ERC) to continue her line of research.
The research in the “Molecular Targeted Therapies” group is focused on the development and evaluation of improved therapies that are directed to relevant molecular targets. Understanding the biological role of molecular targets - that are particularly relevant in certain diseases - is essential to design and develop effective targeted therapies. In cancer, for instance, the epidermal growth factor receptor (EGFR) is a recognized target for cancer imaging and therapy. Current therapies (e.g. photodynamic therapy, chemotherapy) can be ameliorated by improving their selectivity to cancer cells using vehicles that guide them to relevant targets on these cells. Targeting moieties or targeted nanoparticles are possibilities of such vehicles. Nanobodies are the targeting moiety employed in this research group and correspond to small antibody fragments derived from heavy chain antibodies that exist in animals from the camelidae family.
Currently, the main focus of this small team is on rendering photodynamic therapy (PDT) more selective to cancer cells using nanobodies. PDT is a treatment option which makes use of a laser light (harmless on its own) to locally activate a chemical (i.e. photosensitizer) and produce reactive oxygen species that are toxic to cells. Although PDT is nowadays used in some hospitals to treat cancer, it is not a standard treatment. One of the reasons for this is the limited selectivity of the treatment, which employs hydrophobic photosensitizers that can interact with all cell types. Dr. Oliveira has introduced nanobody-targeted PDT, making use of the small size and great binding specificity of nanobodies to specifically target more hydrophilic photosensitizers to cancer cells and kill these specifically. Two of the objectives of the current research are: a) to better understand the mechanism of this new therapeutic approach, in particular its effects on, and the involvement of the immune system, and b) to evaluate this approach in larger animals (e.g. dogs that enter the clinic with cancer), to understand the chances of this treatment to be effective also in humans. Overall, rendering PDT more selective to cancers cells could greatly improve its current clinical application and thereby increase therapeutic options for cancer patients.
- Vida Mashayekhi (PhD student)
- Irati Beltran Hernandez (PhD student)
- Dr. Yingxin Yu (Postdoc)
Cell Biology, Department of Biology, H. R. Kruyt building, N510, (Mon, Wed, Fri)
Pharmaceutics, Department of Pharmaceutical Sciences,
David de Wied building, 3.86 (Tue, Thu)
Post: Padualaan 8, 3584 CH Utrecht, The Netherlands
Tel: +31 6 34 10 34 60
- van Driel PB, Boonstra MC, Slooter MD, Heukers R, Stammes MA, Snoeks TJA, de Bruijn HS, van Diest PJ, Vahrmeijer AL, van Bergen en Henegouwen PMP, van de Velde CJH, Löwik CWGM, Robinson DJ, Oliveira S (2016): EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer, J Control Release 229, 93-105
- Kijanka MM, van Brussel AS, van der Wall E, Mali WP, van Diest PJ, van Bergen En Henegouwen PM, Oliveira S (2016): Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization, EJNMMI Res. 6(1):14
- Heukers R, van Bergen En Henegouwen PM, Oliveira S (2014): Nanobody-photosensitizer conjugates for targeted photodynamic therapy, Nanomedicine, 10(7):1441-51
- Oliveira S, Heukers R, Sornkom J, Kok RJ, van Bergen En Henegouwen PM (2013): Targeting tumors with nanobodies for cancer imaging and therapy, J Control Release, 172(3):607-17
- 2012: VENI Grant NWO-STW - Effective tumor-targeted and image-guided photodynamic therapy
- 2016: ERC Starting Grant - Nanobody-targeted photodynamic therapy to kill cancer