Extravasation of nanoparticles in tumor models (2)
Medication of solid tumors by encapsulation the drug into nanoparticles is a hot topic due to nanoparticles offering targeting through the enhanced permeability and retention effect and often reduced toxicity in nano formulations compared to the traditional formulation. In a previous set of experiments (FOTS 7576) it was found indications that this effect could be predicted using ultrasound imaging of the tumor during injection of microbubbles. Also it was found that kTrans from MRI, a parameter expected to correlate with nanoparticle extravasation did not do so.
These results are both novel and could lead to new understanding in diagnosis and decision-making in patients with solid tumors.
In the experiments here applied for, we want to pursue this topic by both expanding the selection of growth criteria for the tumor models, and to include multiple different nanoparticles. Also, in a subgroup of the animals, kTrans-measurements using MRI will be performed. Tumors will be grown on the hind leg of female Balb/c nude mice and imaged using MRI or contrast enhanced ultrasound. Subsequently, nanoparticles will be injected an allowed to circulate for 6-48 hours and imaged using whole animal optical imaging and near infrared dyes. The animals will then be euthanised and the tumors sectioned for confocal fluorescence imaging.
In the experiment as a total it will be applied for 70 animals. However, the experiment will be performed in a step by step manner, and stopped if the results as seen after FOTS 7576 can not be repeated.
All methods used in the experiments (tumor models, imaging modalities etc.) was used also in FOTS 7576, and no adverse behaviour of the animals was observed as a cause of either the implanted tumor nor the injection of nanoparticles.
In this study some new nanoparticles will be included, but these have all been used in other experiments and been shown safe to the animals. This include PACA NPs and liposomes.
The three R's will be followed in this experiment by doing the experiments in a step-wise manner and only include a subset of the animals at the time. Reduction is fulfilled by this experiment being a follow-up to a previous pilot where only the most promising leads are followed. Refinement is being done by using previously tested protocols and having personnel trained at doing these experiments.
These results are both novel and could lead to new understanding in diagnosis and decision-making in patients with solid tumors.
In the experiments here applied for, we want to pursue this topic by both expanding the selection of growth criteria for the tumor models, and to include multiple different nanoparticles. Also, in a subgroup of the animals, kTrans-measurements using MRI will be performed. Tumors will be grown on the hind leg of female Balb/c nude mice and imaged using MRI or contrast enhanced ultrasound. Subsequently, nanoparticles will be injected an allowed to circulate for 6-48 hours and imaged using whole animal optical imaging and near infrared dyes. The animals will then be euthanised and the tumors sectioned for confocal fluorescence imaging.
In the experiment as a total it will be applied for 70 animals. However, the experiment will be performed in a step by step manner, and stopped if the results as seen after FOTS 7576 can not be repeated.
All methods used in the experiments (tumor models, imaging modalities etc.) was used also in FOTS 7576, and no adverse behaviour of the animals was observed as a cause of either the implanted tumor nor the injection of nanoparticles.
In this study some new nanoparticles will be included, but these have all been used in other experiments and been shown safe to the animals. This include PACA NPs and liposomes.
The three R's will be followed in this experiment by doing the experiments in a step-wise manner and only include a subset of the animals at the time. Reduction is fulfilled by this experiment being a follow-up to a previous pilot where only the most promising leads are followed. Refinement is being done by using previously tested protocols and having personnel trained at doing these experiments.