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. In July 2016, Sabrina was appointed Assistant Professor, and in May 2019 Associate Professor, with a shared position between the division of Cell Biology, Neurobiology and Biophysics, department of Biology and the division of Pharmaceutics, department of Pharmaceutical Sciences.
The research in Oliveira’s 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.
Nanobody-targeted photodynamic therapy
One of the main focuses 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.
Take a look at the article on our KILLCANCER project on the 1st issue of the EDMA’s Project Repository Journal (dissemination of European Research Projects)
Nanobodies for imaging and therapy
Nanobodies are very promising tracers, as they can a. distribute very rapidly through tissues, b. be retained at the tumor, and c. be cleared when unbound, thereby allowing tumor detection 1-2 h post injection. Although some characteristic of an ideal tracer (such as rapid distribution and rapid clearance) are not shared with characteristics of an ideal drug (preferably, long tumor retention and long half-life), within Cell Biology division and together with Dr. van Bergen en Henegouwen, we have been investigating approaches to more efficiently convert a good tracer into a targeted therapy.
Nanobodies have been employed conjugated to the surface of several types of nanocarriers (liposomes, polymeric nanoparticles, micelles, etc) to promote specific cell uptake and allow the delivery of drugs into the target cells. This research is mostly performed in collaboration with colleagues from the Pharmaceutics group, namely Prof. Hennink and Dr. van Nostrum.
- Postdoc: Irati Beltrán Hernández firstname.lastname@example.org
- PhD Student: Bárbara Mesquita email@example.com
- PhD Student: Iris Swart firstname.lastname@example.org (Biology)
- Technician: Alessia Di Maggio email@example.com (Biology)
- Past members: Vida Mashayekhi
Cell Biology, Neurobiology and Biophysics, Department of Biology, H. R. Kruyt building, Z511 (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
Xenaki KT, Dorrestijn B, Muns JA, Adamzek K, Doulkeridou S, Houthoff H, Oliveira S, van Bergen en Henegouwen PMP. Homogeneous tumor targeting with a single dose of HER2-targeted albumin-binding domain-fused nanobody-drug conjugates results in long-lasting tumor remission in mice. Theranostics 2021; 11(11):5525-5538. DOI:10.7150/thno.57510
Deken MM, Kijanka MM, Beltrán Hernández I, Slooter MD, de Bruijn HS, van Diest PJ, van Bergen En Henegouwen PMP, Lowik CWGM, Robinson DJ, Vahrmeijer AL, Oliveira S., Nanobody-targeted photodynamic therapy induces significant tumor regression of trastuzumab-resistant HER2-positive breast cancer, after a single treatment session. J Control Release. 2020, 323:269-281; DOI: 10.1016/j.jconrel.2020.04.030
Beltrán Hernández I, Angelier ML, Del Buono D'Ondes T, Di Maggio A, Yu Y, Oliveira S, The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses. Cancers (Basel). 2020, 12(4):978. doi: 10.3390/cancers12040978.
Liu Y, Scrivano L, Peterson JD, Fens MHAM, Hernández IB, Mesquita B, Toraño JS, Hennink WE, van Nostrum CF, Oliveira S, EGFR-Targeted Nanobody Functionalized Polymeric Micelles Loaded with mTHPC for Selective Photodynamic Therapy. Mol Pharm. 2020, 17(4):1276-1292. doi: 10.1021/acs.molpharmaceut.9b01280
Martínez-Jothar L, Beztsinna N, van Nostrum CF, Hennink WE, Oliveira S, Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination with Photochemical Internalization. Mol Pharm. 2019, ;16(4):1633-1647. doi: 10.1021/acs.molpharmaceut.8b01318
- 2019: KWF High Risk Project – Exploring the systemic immune effects of a selective and local cancer therapy
- 2019: ERC Proof of Concept – Getting ready to treat human patients with nanobody-targeted photodynamic therapy
- 2016: ERC Starting Grant - Nanobody-targeted photodynamic therapy to kill cancer
- 2012: VENI Grant NWO-STW - Effective tumor-targeted and image-guided photodynamic therapy