Comparing the self-assembly of amphiphilic di- and tri-block copolymers with the same hydrophilic hydrophobic ratio

Enzymes display great promise as triggers for disassembly of nanocarriers, thanks to their observed over-expression in specific diseases. The rate of disassembly of these nanocarriers can be highly affected by the accessibility of the enzyme to its substrates. In recent years Roey Amir’s research group has developed a highly modular design of amphiphilic polymer-dendron hybrids, composed of linear hydrophilic polyethyleneglycol (PEG) block and a hydrophobic enzyme-responsive dendron. Hereby, we applied this platform to compare between two hybrids with highly precise structural-changes, in order to examine how changing the architecture of the amphiphilic polymers, from di-block to tri-block, while preserving the same hydrophilic/ hydrophobic ratio, would affect the self-assembly and the enzymatic degradation rates of the formed polymeric structures. We were able to demonstrate that the architectural change indicated above can lead to extreme changes in both the self assembly and the rate of degradation. We observed a major size difference in the self assembled structures; the di-block polymer self-assembled into nanometric structures while the tri-block polymers self-assembled into micrometric structures. Furthermore, upon addition of the activating enzyme the di-block polymeric structure disassembled relatively fast (4.5 hrs) compared to the significantly slow degradation of the tri-block, polymeric structure.
This detailed molecular study enriched our fundamental perception of enzyme-responsive platforms, which can be potentially applied to create smart drug delivery platforms with modified degradation rates using well defined changes of the polymeric architecture.