Well-defined block copolymers composed of a rigid poly(γ-benzyl-L-glutamate) (PBLG) sequence and a poly [2-(dimethylamino)ethyl methacrylate] (PDMAEMA) block were synthesized by Huisgen's 1,3-dipolar cycloaddition (click chemistry) from homopolymers containing azide and alkyne functionalities. These functional groups were introduced in the R-position of both PBLG and PDMAEMA precursors using appropriate R-ω-functionalized initiators to trigger the living/controlled polymerization of the corresponding monomers. Both R-alkyne-and R-azido-PBLGs were synthesized by ring-opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride at room temperature from amino-containing R-alkyne and R-azide difunctional initiators, using dimethylformamide as solvent. As for R-alkyne-PDMAEMA and R-azido-PDMAEMA, they were obtained by copper-mediated atom transfer radical polymerization of 2-(dimethylamino)ethyl methacrylate at 60°C in tetrahydrofuran as solvent. The copper(I)-catalyzed 1,3-dipolar cycloaddition coupling reactions of the R-azido-PBLG with the R-alkyne-PDMAEMA, in the one hand, and of the R-alkyne-PBLG with the R-azido-PDMAEMA, on the other hand were conveniently performed in DMF, affording the targeted PBLG-b-PDMAEMA diblock copolymers. Removal of the residual PDMAEMA used in slight excess was facilitated by the retention of this homopolymer onto the stationary phase of the column chromatography. On the basis of size exclusion chromatography, IR and NMR analyses, click chemistry was found to be quantitative, yielding for the first time hybrid diblock copolymers based on a polypeptide and a vinylic polymer.

The aqueous solution behavior of novel polypeptide-based double hydrophilic block copolymers (DHBCs), namely, poly[2-(dimethylamino)ethyl methacrylate]-b-poly(glutamic acid) (PDMAEMA-b-PGA), exhibiting pH- and temperature-responsiveness is presented using a combination of scattering techniques (light and neutron) and transmission electron microscopy. Close to the isoelectric point (IEP), direct or inverse electrostatic polymersomes are generated by electrostatic interactions developing between the two charged blocks and driving the formation of the hydrophobic membrane of the polymersomes, with the latter being stabilized in water by uncompensated charges. Under basic conditions, that is, when PDMAEMA is uncharged, the thermosensitivity of the DHBCs relates to the lower critical solution temperature (LCST) behavior of PDMAEMA around 40 degrees C. As a consequence, at pH = 11 and below this LCST, free chains of DHBC unimers are evidenced, while above the LCST the hydrophobicity of PDMAEMA drives the self-assembly of the DHBCs in a reversible manner. In this case, spherical polymeric micelles or polymersomes are obtained, depending on the PGA block length. These possibilities of variation in size and shape of morphologies that can be achieved as a function of temperature and/or pH variations open new routes in the development of multiresponsive nanocarriers for biomedical applications.