Forsøksdyr: Biodistribution and efficacy studies of Chitosan-photosensitiser nanoconjugates encapsulating anticancer drugs.

Godkjenningsdato 04.01.2018

Godkjenningsperiode 04.01.2018-03.01.2022

Anticancer drug delivery through biodegradable nanoparticles (NPs), triggered to release their content in the vicinity of the tumor is supposed to enhance the local concentration of drugs and to reduce the side effects. We have developed biodegradable chitosan-photosensitizer (PS) NPs loaded with cytostatic drugs (approved for clinical use). The NPs have been characterized and display good physiochemical properties and high drug loading capacity and drug retainment. They have been tested for uptake and drug release and cytotoxicity in cell culture with and without light-induced photochemical internalization (PCI), and it is now necessary to test their efficacy in vivo. In this study we want to investigate if incorporation of cytostatic drugs can inhibit breast/ colorectal cancer tumor growth and reduce adverse effects in healthy tissue when compared to drug alone. In addition we want to test if the light-induced photodynamic therapy/internalization can further increase the delivery of the nanoparticles to the tumor cells and thereby enhance the anti-tumor effect of the drugs.

The mice will get subcutaneous tumors and be subjected to anticancer drug treatment. This can result in loss of body weight. If we observe any signs of severe symptoms, we will limit harm to the animals to as short time as possible. Previous experiments have shown that the laser illumination treatment and the imaging is well tolerated.

We apply for a total of 433 athymic nude mice that will be used to investigate biodistribution, toxicity and anti tumor efficacy.

For the mice in the treatment experiment it will be Lett belastende . The mice will be given sc and iv injection, but they are few and quickly performed. The mice will also be handled (fysisk fengsling) to measure the tumor size but this is also quickly done. For the mice used to find MTD the experiment will be betydlig belastende. In order to find MTD some mice might get a dose higher than what is tolerable, and can then show adverse effects. When this is observed the mice will be sacrificed so that the suffering will be as short as possible.