An electronic copy of the thesis may be ordered from the faculty up to 2 days prior to the public defence. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Jutta Horejs-Hoeck, Paris-Lodron Universität
- Second opponent: Professor Lars Herfindal, University of Bergen
- Third member and chair of the evaluation committee: Professor Anne Simonsen, University of Oslo
Chair of the Defence
Professor Øyvind Bruland, Faculty of Medicine, University of Oslo
Principal Supervisor
Head of Department Gunhild M. Mælandsmo, Oslo University Hospital
Summary
According to the world health organization, breast cancer is the most common type of cancer in women. Among other subtypes, triple-negative breast cancer is one of the most aggressive subtypes and presents challenges in the treatment. Chemotherapy is the most widely used treatment modality, but adverse effects; short circulation time and development of resistance are major issues with the treatment.
Nanoparticles (NPs) have many applications in medicine, including therapy, imaging, diagnostics and theranostics. Some cancer-specific characteristics allow NPs to passively enter and retain in the tumor. NPs also facilitate other cancer-targeting approaches. In recent years, NPs are explored as vehicles for drug delivery in cancer treatment due to their benefits over conventional chemotherapy, such as improved pharmacokinetics and reduced toxicity.
The primary aim of the thesis was to investigate drug delivery by biodegradable NPs as an alternative for conventional chemotherapy (as a free drug). Pre-clinical experiments using human cancer cell lines or patient-derived tumors grown in immunodeficient mice were performed. Upon NP-based chemotherapeutic drug delivery, we assessed growth retardation and tumor infiltration of the most common immune cells (marcophages), and compared these with conventional chemotherapy.
We observed that NP-based drug delivery improved treatment efficacy compared to free chemotherapeutic drugs. We also showed that NP-based drug delivery approaches could safely deliver high payload of chemotherapeutic drugs, and that prolonged circulation time was achieved. We assessed biodistribution of NPs in different organs and in tumor tissue. Moreover, we showed that NP-based drug delivery enhanced infiltration of anti-tumorigenic macrophages, and reduced infiltration of pro-tumorigenic macrophages that might explain the improved treatment efficacy.
Our findings indicate that NP-based drug delivery present attractive alternative to conventional chemotherapy.
Additional information
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