Enzymatically Degradable Self-Reporting Micelles

Enzyme responsive micelles have gained increased interest in recent years due to their high potential in different field`s ranging from smart materials to drug delivery. Our group has recently developed a highly modular platform of enzymatically degradable polymeric micelles. These micelles are composed of self-assembled amphiphilic hybrids of hydrophilic polyethyleneglycol (PEG) block and a dendron functionalized with enzymatically cleavable hydrophobic end-groups. The need for new methods for drug delivery and imaging probes led us to develop the next generation of labeled smart micelles that can self-report their structural changes by spectral response. Here we present a novel design of covalently labeled enzyme-responsive amphiphilic hybrids that can report the self-assembly and disassembly of the micelles by changes in the dyes` spectral properties. These spectral changes occur due to alteration of dye-dye interactions caused by the supramolecular structural changes of the micelles. By simply changing the labeling dyes, we demonstrate different spectral activities (turn-On or spectral-switch of the spectral signal ^[1]) that are generated due to different dye-dye interactions, such as, excimer formation, self-quenching or FRET. This highly modular approach opens the way for new delivery platforms that allow advanced methods for imaging and tracking the degree and location of drug released.

[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.