Forsøksdyr: Treatment of brain metastases using nanoparticles

Godkjenningsdato 03.04.2020

Godkjenningsperiode 03.04.2020-03.04.2023

1. Background
Brain metastasis is associated with extremely poor patient prognosis, and current treatments are not effective. In order to study cancer metastasis, more appropriate preclinical models are needed. We have established a unique human metastasis model for studying metastatic progression, where we inject human metastatic tumor cells into the left cardiac ventricle of immunodeficient mice. We have done a detailed characterisation of the blood-brain barrier (BBB) in the tumor model. We are currently sharing our model and knowledge with several other research groups (in UK, Germany, USA, The Netherlands).

We have preliminary in vitro data, showing a very good effect on melanoma brain metastasis cell lines in cell culture when they are treated with mesophorous silica nanoparticles loaded with drugs.

2. Aim of the research
We will treat tumor bearing animals with mesophorous silica nanoparticles loaded with either doxorubicin or sorafenib. The aim of this project is to bring our research into a phase 1 clinical trial on cancer metastasis patients. The current application thus describes a set of important experiments, in order to achieve this.

3. Expected harm to the animals
None. The nanoparticles is non-toxic. Doxorubicin and sorafenib have been used extensively in animal experiments as well as in patients. The drug toxicities are therefore well characterised, and we will administer drug doses below toxic values to the animals.

4. Expected benefit for science and society
If successful, we hope to achieve a new and better treatment of cancer patients with metastatic spread to the brain.

5. How many and kind of animals to be used
We plan to use up to a total of 138 nod/scid mice in our experiments.

6. How the demand on RRR is to be achieved
We need to use animal models in our research, as in vitro models do not reflect the 3d structural behavior and physiological conditions in animals, and these conditions are crucial for metastatic spread of cancers in patients. Therefore, we are of the opinion that in vitro experiments are not sufficient to obtain our aim, which is to bring new treatment into the clinic.
Refinement: The injection techniques used, is causing mild harm to the animals. We use 2 trained people during the injections, one responsible for the injections, and the other responsible for animal care. The animals are placed onto a heating pad, and we use ultrasound guidance during intracardiac injections, which ensure fast and accurate injections. During imaging, two trained persons are present, one to prepare and monitor the animals, and the other to operate the imaging instrumentation. Heating is used. The imaging procedures do not cause any harm to the animals.