Synthesis of well-defined poly(N-isopropylacrylamide)-b-poly(L-glutamic acid) by a versatile approach and micellization

A novel Fmoc-protected chain transfer agent (CTA) was synthesized and applied in the reversible addition-fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAAm), resulting in well-defined Fmoc-protected PNIPAAm and the amino-end capped PNIPAAm by the subsequent hydrolysis. Poly(N-isopropylacrylamide)-b-poly(l-glutamic acid) (PNIPAAm-b-PLGA) with controlled molecular weight and narrow molecular weight distribution was synthesized successfully via ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydrides (NCAs) by using PNIPAAm-NH2 as the macroinitiator. Both pH- and thermo-responsive micellization behaviors of the block copolymer PNIPAAm55-b-PLGA35 in dilute aqueous solution were investigated by means of the pyrene fluorescence, circular dichroism, 1H NMR, transmission electron microscopy and dynamic and static light scattering. Spherical PLGA-core and rod-like PNIPAAm-core micelles are formed in response to pH and temperature. The reversible transition between the PLGA-core and PNIPAAm-core micelles was observed. This work provides a versatile approach for synthesizing well-defined stimuli-responsive polypeptide-based double hydrophilic diblock copolymers (DHBCs), and is of great potential for generating useful stimuli-responsive materials in biomedical applications.