Improving targeting drug delivery for clinical nanomedicine
For successful application of targeted NPs in future diagnostic and therapeutic settings, it is crucial to understand NP targeting efficiency and dynamics and relate these to NP design on one side and target availability on the other. Although the project has only just started, I have 1. Established synthesis of targeted liposomes and emulsions at NTNU. 2. Been fully trained to do animal experiments. 3. Admitted to the PhD program Medical Technology. 4. Initiated the first in vivo work Although the first clinical trials with targeted nanomedicine are underway, their interaction with biology is highly dynamic and remains poorly understood. In this project we aim to imporve our understanding of this complex in vivo nanoparticle behavior. In vivo targeting efficiency and kinetics will be characterized and quantified at the cellular level using dynamic intravital microscopy and at the whole organ level using dynamic magnetic resonance imaging (MRI). We have performed the first in vivo microscopy experiments with highly interesting results. The combination with MRI is anticipated to provide us with novel and quantitative understanding of in vivo NP targeting, which will be valuable for targeted image guided drug delivery and molecular imaging in general. By incorporating MRI in our effort, we will obtain insights in how NP targeting dynamics affect image contrast in this clinical modality. The main objectives of the project are: • Develop nanoparticles which efficiently target tumor vasculature • Quantify nanoparticle targeting and target levels with clinically relevant imaging modalities To achieve these objectives we have defined three specific aims: 1. Develop targeted lipid-based nanoparticles. 2. Characterize and quantify NP targeting kinetics at the cellular level in vivo using dynamic intravital microscopy. 3. Characterize and quantify NP targeting kinetics at the whole organ level in vivo using dynamic MRI.