Delivery system in micellar form having modular spectral response based on enzyme-responsive amphiphilic PEG-dendron hybrid polymers

Abstract

The present invention relates to new molecular design that allows micelles to report their activation and disassembly by an enzymatic trigger. The molecular design is based on introduction of a labeling moiety selected from a fluorescent dye, a dark quencher, combinations of dyes or dyes/quenchers, and a fluorinated moiety (a 19F-magenetic resonance (MR) probe for turn ON/OFF of a 19F-MR signal) through covalent binding to the focal point of amphiphilic polymer-dendron hybrids with the labeling moiety. At the assembled micellar state, the dyes are closely packed and hence the probability for intermolecular interactions increases significantly, leading to alteration of the fluorescent properties (signal quench or shift) or the 19F-MR signal (OFF state) of the micelles. Upon enzymatic cleavage of the hydrophobic end-groups from enzyme-responsive dendron, the polymers become hydrophilic and disassemble. This structural change is then translated into a spectral change as dye-dye interactions are halted and the dyes regain their intrinsic fluorescent properties, or alternatively by turn ON the 19F-MR signal. The high modularity of the design allows the introduction of various types of dyes and thus enables rational adjustment of the spectral response. Two major types of responses are described: Turn-On/Off and spectral shift, depending on the type of labeling dye. The present invention further provides methods of use of the hybrid delivery system and to a kit comprising the same.

Dependencies are inferred from the claim text.