Periodic Reporting for period 1 - NoBiasFluors (Non-biased fluorescent dyes as markers of drugs for optical in cellulo and in vivo imaging)
Période du rapport: 2020-01-01 au 2022-12-31
Fluorescence imaging of biological processes in live animals is an excellent non-invasive bioanalytical tool. Due to the intrinsic properties of biological tissues, only red-fluorescing dyes can be used for the imaging. Currently available dyes of this type exhibit important disadvantages including their clear bias towards particular intracellular organelles, for example mitochondria. Therefore, distribution of drug~dye conjugates in live animals is often dominated by the dye, rather than by the drug. The problem is especially prominent if the drug is a low-molecular weight compound. The majority of currently used in clinics drugs are compounds of such type. NoBiasFluors works on solving this problem by developing non-biased red-fluorescing dyes suitable for in vivo imaging of distribution of low molecular weight drugs. If the goal is achieved, it will allow substantial expanding our knowledge on the mode of action of typical drugs.
From the beginning of the project we’ve performed screening of several pH sensitive dyes for the formation of supramolecular assemblies with the output for the reducing their toxicity and improve water solubility properties. Besides, the ability of the newly prepared assemblies to target and fluorescently label cell acidic organelles (lysosomes and mitochondria) was also tested. Additionally, the ability of the supramolecular assemblies to form well-formed aggregations depending on the structure of the fluorescent compound was also investigated.
We have already identified red-fluorescing BIDIPY-derivatives, which are non-biased dyes suitable for labelling of anticancer aminoferrocene based prodrugs with molecular weight below 1000 Da.
We have already identified red-fluorescing BIDIPY-derivatives, which are non-biased dyes suitable for labelling of anticancer aminoferrocene based prodrugs with molecular weight below 1000 Da.
The research performed within the reported publication represented an important step in understanding the behavior of fluorescent entities inside the living cell. Prolonged monitoring of the fluorescent response (over 48 hours) of the investigated living cells gave insights into the mechanism of fluorescent dyes intracellular migration and specific accumulations. The stability of the fluorescent signal and, particularly the increase in fluorescence in time due to the pH dependence nature of the investigated dyes also furnished valuable information for the successful implementation of the current project.