In this work, the synthesis and characterization of novel amphiphilic diblock copolymers of poly(2-dimethylamino ethyl methacrylate)-b-poly(lauryl methacrylate), PDMAEMA-b-PLMA, using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique, are reported. The diblocks were successfully derivatized to cationic and zwitterionic block polyelectrolytes by quaternization and sulfobetainization of the PDMAEMA block, respectively. Furthermore, their molecular and physicochemical characterization was performed by using characterization techniques such as NMR and FTIR, size exclusion chromatography, light scattering techniques, and transmission electron microscopy. The structure of the diblock micelles, their behavior, and properties in aqueous solution were investigated under the effect of pH, temperature, and ionic strength, as PDMAEMA and its derivatives are stimuliresponsive polymers and exhibit responses to variations of at least one of these physicochemical parameters. These new families of stimuli-responsive block copolymers respond to changes of their environment giving interesting nanostructures, behavioral motifs, and properties, rendering them useful as nanocarriers for drug delivery and gene therapy.

The Langmuir film balance technique was used to investigate the effects of copolymer composition and subphase pH/temperature on the aggregation behaviors of two stimuliresponsive amphiphilic diblock copolymers poly(2-(dimethylamino)ethyl methacrylate)-block-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) at the air/water interface. The morphologies of their Langmuir−Blodgett (LB) films were characterized by atomic force microscopy. With the rise in subphase pH, the corresponding surface pressure−molecular area isotherms of the two copolymers gradually move to large areas due to the decreased protonation degrees of PDMAEMA blocks. Almost all the LB films of the predominantly hydrophilic copolymer prepared under different subphase conditions exhibit isolated circular micelles. For the predominantly hydrophobic copolymer, however, the dense wormlike aggregates and the large domains appear in its LB films due to the connection of adjacent PLMA cores at low temperature and the local richness of PDMAEMA chains at high temperature, respectively.

Physicochemical characteristics and biological performance of polyplexes based on two identical copolymers bearing tertiary amino or quaternary ammonium groups are evaluated and compared. Poly(2‐(dimethylamino)ethyl methacrylate)‐b‐poly(oligo(ethylene glycol) methyl ether methacrylate) block copolymer (PDMAEMA‐b‐POEGMA) is synthesized by reversible addition fragmentation chain transfer polymerization. The tertiary amines of PDMAEMA are converted to quaternary ammonium groups by quaternization with methyl iodide. The two copolymers spontaneously formed well‐defined polyplexes with DNA. The size, zeta potential, molar mass, aggregation number, and morphology of the polyplex particles are determined. The parent PDMAEMA‐b‐POEGMA exhibits larger buffering capacity, whereas the corresponding quaternized copolymer (QPDMAEMA‐b‐POEGMA) displays stronger binding affinity to DNA, yielding invariably larger in size and molar mass particles bearing greater number of DNA molecules per particle. Experiments revealed that QPDMAEMA‐b‐POEGMA is more effective in transfecting pEGFP‐N1 than the parent copolymer, attributed to the larger size, molar mass, and DNA cargo, as well as to the effective cellular traffic, which dominated over the enhanced ability for endo‐lysosomal escape of PDMAEMA‐b‐POEGMA.

There is an emerging need to evolve the conventional lyotropic liquid crystalline nanoparticles to advanced stimuli-responsive, therapeutic nanosystems with upgraded functionality. Towards this effort, typically used stabilizers, such as Pluronics®, can be combined or replaced by smart, stimuli-responsive block copolymers. The aim of this study is to incorporate the stimuli-responsive amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) as a stabilizer in lipidic liquid crystalline nanoparticles, in order to provide steric stabilization and simultaneous stimuli-responsiveness. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by light scattering techniques, cryogenic-transmission electron microscopy (cryo-TEM), X-ray diffraction (XRD) and fluorescence spectroscopy. The PDMAEMA-b-PLMA, either individually or combined with Poloxamer 407, exhibited different modes of stabilization depending on the lipid used. Due to the protonation ability of PDMAEMA blocks in acidic pH, the nanoparticles exhibited high positive charge, as well as pH-responsive charge conversion, which can be exploited towards pharmaceutical applications. The ionic strength, temperature and serum proteins influenced the physicochemical behavior of the nanoparticles, while the polymer concentration differentiated their morphology; their micropolarity and microfluidity were also evaluated. The proposed liquid crystalline nanosystems can be considered as novel and attractive pH-responsive drug and gene delivery nanocarriers due to their polycationic content.