10.1021/ja510085s.s001 Ido Rosenbaum Ido Rosenbaum Assaf J. Harnoy Assaf J. Harnoy Einat Tirosh Einat Tirosh Marina Buzhor Marina Buzhor Merav Segal Merav Segal Liat Frid Liat Frid Rona Shaharabani Rona Shaharabani Ram Avinery Ram Avinery Roy Beck Roy Beck Roey J. Amir Roey J. Amir Encapsulation and Covalent Binding of Molecular Payload in Enzymatically Activated Micellar Nanocarriers American Chemical Society 2015 loading strategy Covalent Binding cargo covalently encapsulated noncovalent encapsulation probe molecules Enzymatically Activated Micellar NanocarriersThe PEG payload capacities hybrid enzyme release rate core release rates covalent encapsulation micelle Molecular Payload encapsulated noncovalently micellar nanocarrier polyethylene glycol loading capacity type micellar nanocarriers amphiphilic dendron 2015-02-18 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Encapsulation_and_Covalent_Binding_of_Molecular_Payload_in_Enzymatically_Activated_Micellar_Nanocarriers/2194936 The high selectivity and often-observed overexpression of specific disease-associated enzymes make them extremely attractive for triggering the release of hydrophobic drug or probe molecules from stimuli-responsive micellar nanocarriers. Here we utilized highly modular amphiphilic polymeric hybrids, composed of a linear hydrophilic polyethylene glycol (PEG) and an esterase-responsive hydrophobic dendron, to prepare and study two diverse strategies for loading of enzyme-responsive micelles. In the first type of micelles, hydrophobic coumarin-derived dyes were encapsulated noncovalently inside the hydrophobic core of the micelle, which was composed of lipophilic enzyme-responsive dendrons. In the second type of micellar nanocarrier the hydrophobic molecular cargo was covalently linked to the end-groups of the dendron through enzyme-cleavable bonds. These amphiphilic hybrids self-assembled into micellar nanocarriers with their cargo covalently encapsulated within the hydrophobic core. Both types of micelles were highly responsive toward the activating enzyme and released their molecular cargo upon enzymatic stimulus. Importantly, while faster release was observed with noncovalent encapsulation, higher loading capacity and slower release rate were achieved with covalent encapsulation. Our results clearly indicate the great potential of enzyme-responsive micellar delivery platforms due to the ability to tune their payload capacities and release rates by adjusting the loading strategy.