Development of Inflammation Responsive Fluorinated Oxalate Compounds for Theragnostic Applications

​Grant funding 2022-2024
Ministry of Education and Sciences

We will develop nanomedicines of ROS degradable fluorinated compounds with hydrophobic drugs that give rise to release the drugs and tune-on multimodal (CL, US, MR) bioimaging signals at the same location where they meet with a high level of ROS in the inflammatory region.

With recent parallel advances on the molecular-based understanding of diseases and drug delivery systems for diagnosis and therapy, there have been various researches for developing a smart nanocarrier that can release loaded pharmaceuticals and/or diagnostic probes into a targeted tissue as a response for bi-omarkers. Reactive oxygen species (ROS) are high-energy oxygen-bearing molecules that are biomarkers of aging and inflammation. Accordingly, ROS-mediated imaging and drug release can be of great interest in ‘theranostics (therapy + diagnosis)’, which is the recently emerging technology.

In this project, we will develop theranostic nanomedicine, which image inflammatory disease as well as actively deliver drugs in that place, simultaneously. ROS is regarded as the main stimulus for displaying an inflamed tissue with the switchable multimodal bioimaging including CL, US, and 19F MRI and for ac-tive delivery of hydrophobic drugs. Co-encapsulation of ROS degradable fluorinated oxalate compounds with hydrophobic drugs will give rise to a tune-on the multiple imaging modality and release the drugs at the same location where the compounds meet with the high level of ROS.

The specific objectives are:
1) Development of a novel class of ROS degradable fluorinated oxalate compounds which is hydrophobic in the pre-degradation state and hydrophilic in the post-degradation state by ROS;
2) Fabrication of biocompatible nanoparticles, loading the newly developed fluorinated oxalate compounds and hydrophobic drugs;
3) Development of a novel class of ROS degradable fluorinated oxalate polymer nanocarriers which is hy-drophobic in the pre-degradation state and hydrophilic in the post-degradation state by ROS; and
4) Utilization of the novel fluorinated compounds for a theranostic application that performs theranostics of inflammatory diseases

The main outputs expected of these new fluorinated compounds are:
1) Over three units of novel multimodal imaging probes with high on/off ratio responsive to ROS.
2) Over two unit of a novel fluorinated polymer possessing high loading efficiency of anti-inflammatory drugs and high ROS selective degradability.
3) A novel theragnostic technology to diagnose and cure of inflammatory diseases in the early stage.