Enzyme-Responsive Amphiphilic PEG-Dendron Hybrids and Their Assembly into Smart Micellar Nanocarriers

• Published in: Journal of the American Chemical Society 2014-05, Vol.136 (21), p.7531-7534
• Main Authors: Harnoy, Assaf J, Rosenbaum, Ido, Tirosh, Einat, Ebenstein, Yuval, Shaharabani, Rona, Beck, Roy, Amir, Roey J
• Format: Article
• Language: English
• Subjects: Amidohydrolases - chemistry; Amidohydrolases - metabolism; Dendrimers - chemistry; Hydrophobic and Hydrophilic Interactions; Micelles; Molecular Structure; Nanostructures; Polyethylene Glycols - chemistry; Surface-Active Agents - chemical synthesis; Surface-Active Agents - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja413036q

Enzyme-responsive micelles have great potential as drug delivery platforms due to the high selectivity of the activating enzymes. Here we report a highly modular design for the efficient and simple synthesis of amphiphilic block copolymers based on a linear hydrophilic poly­ethylene­glycol (PEG) and an enzyme-responsive hydrophobic dendron. These amphiphilic hybrids self-assemble in water into micellar nanocontainers that can disassemble and release encapsulated molecular cargo upon enzymatic activation. The utilization of monodisperse dendrons as the stimuli-responsive block enabled a detailed kinetic study of the molecular mechanism of the enzymatically triggered disassembly. The modularity of these PEG-dendron hybrids allows control over the disassembly rate of the formed micelles by simply tuning the PEG length. Such smart amphiphilic hybrids could potentially be applied for the fabrication of nanocarriers with adjustable release rates for delivery applications.