The need for selective drug delivery systems requires the development of advanced platforms that can release the drug upon external stimuli and simultaneously report the degree and location of activation. To address this challenge our group has recently developed a platform of labeled enzymatically degradable polymeric micelles. These micelles are formed by self-assembly of amphiphilic hybrids with hydrophilic polyethylene glycol (PEG) block, dendron with enzymatically cleavable hydrophobic end-groups, and a linker that allows covalent labeling. These smart micelles can report their self-assembly and disassembly by tailor-made spectral responses by simply modifying the labeling moiety. We demonstrate different spectral responses, such as turn-On or spectral-switch of the spectral signal that are generated due to different supramolecular dye-dye interactions, such as, excimer formation, self-quenching or FRET, at the assembled state. The high structural precision of our dendritic platform allowed us to systematically tune the hydrophobicity and stability of the micelles by small structural modifications. Utilizing the spectral response of micelles we determined the relation between the stability of the polymeric micelles and their cell entry pathways. These results highlight the crucial rule of minor structural changes in the hydrophobic block when designing effective polymeric nanostructures for drug delivery applications.

Enzymatically degradable self-reporting micellar nanocarriers

2019 Fall National Meeting

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