(511b) Synthesis and Self-Assembly of Bio-Responsive Block Copolymers

We have designed responsive polymeric micelles for targeted drug delivery applications by taking advantage of the self-assembly of amphiphilic block copolymers containing protease-sensitive linkages embedded within their hydrophilic backbones.  These micelles are capable of responding to biological stimuli, as cleavage of the peptide linkages should destabilize the assembled structures and result in the efficient delivery of therapeutic molecules to specific cellular locations.  Our strategy is based on the solution assembly of poly(butadiene-b-ethylene oxide) (PB-PEO).  A non-peptide containing PB-PEO model polymer with M_n = 12,600 g/mol and hydrophilic weight fraction w_philic = 0.66 self-assembles into spherical micelle structures in aqueous solutions.  Because the chain characteristics of this PB-PEO polymer induced micelles formation, we used similar guiding principles in the synthesis of our micelle-forming PB-PEO-peptide conjugates.  Polymer-peptide conjugates were created through a combination of anionic polymerization and solid phase peptide synthesis, and the resulting copolymers were characterized with nuclear magnetic resonance spectroscopy (¹H NMR), gel permeation chromatography (GPC), and mass spectrometry (MALDI-TOF MS).  The aqueous solution-assembly of the PB-PEO-peptide amphiphiles was probed with dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM) experiments.