SPECTRALLY ACTIVE MICELLAR NANOCARRIERS

The need for new imaging probes and delivery platforms requires the development of advanced smart systems that change their structure and spectral properties in response to external stimuli, which allows specific monitoring. To address this challenge we present a new molecular design of labeled enzyme-responsive amphiphilic hybrids that are composed of a linear hydrophilic polyethyleneglycol (PEG) block and an enzymatically responsive dendron as a hydrophobic block. We examine two different imaging approaches by simply changing the labeling moiety of the system either with a fluorescent marker [1] or with a fluorinated group (¹⁹F MR). In aqueous solution, the labeled PEG-dendron hybrids self-assemble into micelles and exhibit an “OFF” signal due to intermolecular dye-dye interactions or the low mobility of the ¹⁹F probes. 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 an “ON” signal of the fluorescent response due to the elimination of the dye-dye interactions or of the ¹⁹F MR caused by increase in the mobility of the ¹⁹F moieties. This highly modular approach enables generation of customized spectral activities in 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 21.44 (2015): 15633-15638.