Design, Synthesis and Applications of Smart Polymeric Amphiphiles

Roey Amir, School of Chemistry, Tel Aviv University, Tel Aviv, Israel
Assaf Harnoy, School of Chemistry , Tel Aviv University, Tel Aviv, Israel
Ido Rosenbaum, School of Chemistry , Tel Aviv University, Tel Aviv, Israel
Marina Buzhor, School of Chemistry , Tel Aviv University, Tel Aviv, Israel
Liat Frid, School of Chemistry, Tel Aviv University, Tel Aviv, Israel
Merav Segal, School of Chemistry, Tel Aviv University, Tel Aviv, Israel
Yael Cohen, School of Chemistry, Tel Aviv University, Tel Aviv, Israel

The need for smart delivery platforms that can release their molecular payload only at the target tissue has motivated the development of stimuli-responsive micelles. Such micelles are designed to disassemble and release their encapsulated cargo upon external stimuli. Among the various types of stimuli that were utilized to trigger the disassembly of such micelles, enzymes offer great potential for the activation of biomedical carriers due to their overexpression in various diseases. In this talk we will report a highly modular design for the simple and efficient synthesis of amphiphilic block copolymers based on a linear hydrophilic polyethyleneglycol (PEG) and an enzyme-responsive hydrophobic dendron. The PEG-Dendron hybrids were synthesized through an accelerated divergent synthetic methodology using a combination of amidation and tiol-yne reactions. These amphiphilic hybrids self-assemble in water into smart micelles that can disassemble and release their encapsulated molecular cargo upon enzymatic activation. The high modularity of these PEG-dendron hybrids offers control over the disassembly rate of the formed micelles by simply tuning of the PEG length. Such smart amphiphilic hybrids could potentially be applied for the fabrication of nanocarriers with adjustable release rates for delivery applications.