Controlled synthesis of β-sheet polymers based on side-chain amyloidogenic short peptide segments via RAFT polymerization

A strategy is documented that exploits the controlled synthesis of side-chain peptide based stimuli-responsive hybrid macromolecules inspired by amyloid based β-sheet forming peptides. Well-defined side-chain peptidic polymers have been synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization technique using a representative methacrylate monomer with a short peptide segment (Leu-Val-Phe) corresponding to the amyloid β-peptide Aβ1–42. Furthermore, the monomethoxy poly(ethylene glycol) (mPEG) macro-chain transfer agent is employed for RAFT polymerization of this peptidic monomer to prepare peptide based amphiphilic nano-carriers, a promising reservoir for hydrophobic Nile red dye or doxorubicin based anticancer drug molecules. These hybrid materials can easily produce primary amino groups in terminals of side-chains that can be protonated or deprotonated by changing the pH of the aqueous medium, thus providing “smart” pH-responsiveness, cationic characteristics and complexation capabilities with DNA to form polyplexes. Circular dichroism (CD) spectroscopy demonstrates the formation of a secondary structure from these peptidic polymers and they adopted the β-sheet conformation, which were stable against heat in the experimental temperature range and solvent polarity. Solid-state FT-IR spectroscopy has been performed to understand the formation of β-sheets as well as to distinguish between their parallel and antiparallel propensity. In vitro cytotoxicity testing indicates the biocompatible nature of these peptidic materials, and confocal laser scanning microscopy (CLSM) images revealed cellular uptake of their drug/dye loaded micelles, which potentially offers them as a suitable candidate with dual bioapplications for drug delivery as well as gene transfer.