SELF-REPORTING ENZYME RESPONSIVE MICELLAR NANOCARRIERS AS DRUG DELIVERY PLATFORM

The need for new fluorescent imaging and delivery platforms requires the development of advanced smart systems that change their structure and fluorescence in response to external stimuli. In this talk we will report a new molecular design of fluorescently labeled enzyme-responsive amphiphilic hybrids with tunable fluorescent responses [1]. These smart hybrids are composed of a linear hydrophilic polyethyleneglycol (PEG) block and an enzymatically responsive dendron as a hydrophobic block. In aqueous solution, the labeled PEG-dendron hybrids self-assemble into micelles and the fluorescence of the dyes is quenched or shifted due to intermolecular dye-dye interactions. Enzymatic cleavage of the hydrophobic end-groups increases the hydrophilicity of the hybrids, leading to disassembly of the micelles. This enzymatically induced structural change is translated into spectral response as the dye-dye interactions are eliminated and the dyes regain their intrinsic fluorescence. We will demonstrate a Turn-On and a spectral shift responses by tuning the type of the labeling dye. This highly modular approach enables generation of customized spectral activity as response to enzymatic activation of non-responsive labeling dyes.

[1] “Supramolecular translation of enzymatically triggered disassembly of micelles into tunable fluorescent responses”, Buzhor, Marina; Harnoy, Assaf J.; Tirosh, Einat; Barak, Ayana; Schwartz, Tal; Amir, Roey J. Chemistry - A European Journal (2015), just accepted.