In this study, we report the synthesis of amphiphilic hyperbranched poly[(2-dimethylaminoethyl methacrylate)-co-(benzyl methacrylate)] statistical copolymers with two different stoichiometric compositions using the reversible addition–fragmentation chain transfer polymerization (RAFT) technique. The selection of monomers was made to incorporate a pH and thermoresponsive polyelectrolyte (DMAEMA) component and a hydrophobic component (BzMA) to achieve amphiphilicity and study the effects of architecture and environmental factors on the behavior of the novel branched copolymers. Molecular characterization was performed through size exclusion chromatography (SEC) and spectroscopic characterization techniques (¹H-NMR and FT-IR). The self-assembly behavior of the hyperbranched copolymers in aqueous media, in response to variations in pH, temperature, and ionic strength, was studied using dynamic light scattering (DLS), electrophoretic light scattering (ELS), and fluorescence spectroscopy (FS). Finally, the efficacy of the two novel copolymers to encapsulate curcumin (CUR), a hydrophobic, polyphenolic drug with proven anti-inflammatory and fluorescence properties, was established. Its encapsulation was evaluated through DLS, UV–Vis, and fluorescence measurements, investigating the change of hydrodynamic radius of the produced mixed copolymer–CUR nanoparticles in each case and their fluorescence emission properties.

This manuscript serves as the starting point for in-depth research of multicomponent, statistical, methacrylate-based copolymers that potentially mimic the behavior of proteins in aqueous solutions. These synthetic macromolecules are composed of specially chosen comonomers: methacrylic acid (MAA), oligoethylene glycol methyl ether methacrylate (OEGMA₄₇₅), 2-(dimethylamino)ethyl methacrylate (DMAEMA) and benzyl methacrylate (BzMA). Monomer choice was based on factors such as the chemical nature of pendant functional groups, the polyelectrolyte/polyampholyte and amphiphilic character and the overall hydrophobic–hydrophilic balance (HLB) of the obtained quaterpolymers. Their synthesis was achieved via a one-pot reversible addition fragmentation chain transfer (RAFT) polymerization in two distinct compositions and molecular architectures, linear and hyperbranched, respectively, in order to explore the effects of macromolecular topology. The resulting statistical quaterpolymers were characterized via ¹H-NMR and ATR-FTIR spectroscopies. Their behavior in aqueous solutions was studied by dynamic (DLS) and electrophoretic light scattering (ELS) and fluorescence spectroscopy (FS), producing vital information concerning their self-assembly and the structure of the formed aggregates. The physicochemical studies were extended by tuning parameters such as the solution pH and ionic strength. Finally, the quaterpolymer behavior in FBS/PBS solutions was investigated to test their colloid stability and biocompatibility in an in vivo-mimicking, biological fluid environment.

Amphiphilic statistical copolymers can be utilized for the formulation of nanocarriers for the drug delivery of insoluble substances. Oligoethylene glycol methylether methacrylate and methyl methacrylate are two biocompatible monomers that can be used for biological applications. In this work, the synthesis of linear poly(oligoethylene glycol methylether methacrylate-co-methyl methacrylate), P(OEGMA-co-MMA), and statistical copolymers via reversible addition fragmentation chain transfer (RAFT) polymerization is reported. P(OEGMA-co-MMA) copolymers with different comonomer compositions were synthesized and characterized by size exclusion chromatography (SEC), ¹H-NMR, and ATR-FTIR spectroscopy. Self-assembly studies were carried out by the dissolution of polymers in water and via the co-solvent protocol. For the characterization of the formed nanoaggregates, DLS, zeta potential, and fluorescence spectroscopy (FS) experiments were performed. Such measurements delineate the association of copolymers into aggregates with structural characteristics dependent on copolymer composition. In order to investigate the drug encapsulation properties of the formed nanoparticles, curcumin and quercetin were loaded into them. The co-solvent protocol was followed for the encapsulation of varying concentrations of the two drugs. Nanocarrier formulation properties were confirmed by DLS while UV–Vis and FS experiments revealed the encapsulation loading and the optical properties of the drug-loaded nanosystems in each case. The maximum encapsulation efficiency was found to be 54% for curcumin and 49% for quercetin. For all nanocarriers, preliminary qualitive biocompatibility studies were conducted by the addition of FBS medium in the copolymer aqueous solutions which resulted in no significant interactions between copolymer aggregates and serum proteins. Novel nanocarriers of curcumin and quercetin were fabricated as a first step for the utilization of these statistical copolymer nanosystems in nanomedicine.

Aggregation-induced emission dyes (AIEs) have gained significant interest due to their unique optical properties. Upon aggregation, AIEs can exhibit remarkable fluorescence enhancement. These systems are ideal candidates for applications in bioimaging, such as image-guided drug delivery or surgery. Encapsulation of AIEs in polymeric nanocarriers can result in biocompatible and efficient nanosystems. Herein, we report the fabrication of novel nanoaggregates formulated by amino terpolymer and tetraphenylethylene (TPE) AIE in aqueous media. Poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA) hydrophilic terpolymer was utilized for the complexation of the sodium tetraphenylethylene 4,4′,4″,4‴-tetrasulfonate AIE dye. Fluorescence spectroscopy, physicochemical studies, and self-assembly in aqueous and fetal bovine serum media were carried out. The finely dispersed nanoparticles exhibited enhanced fluorescence compared to the pure dye. To investigate the role of tertiary amino groups in the aggregation phenomenon, the polymer was quaternized, and quaternized polymer nanocarriers were fabricated. The increase in fluorescence intensity indicated stronger interaction between the cationic polymer analog and the dye. A stronger interaction between the nanoparticles and fetal bovine serum was observed in the case of the quaternized polymer. Thus, P(DEGMA-co-DMAEMA-co-OEGMA) formulations are better candidates for bioimaging applications than the quaternized ones, presenting both aggregation-induced emission and less interaction with fetal bovine serum.

In this work, we report the synthesis of novel triple hydrophilic statistical terpolymers consisting of three different methacrylate monomers with varying degrees of responsivity to solution conditions. Terpolymers of the type poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA), and of different compositions, were prepared by using the RAFT methodology. Their molecular characterization was carried out using size exclusion chromatography (SEC) and spectroscopic techniques, including ¹H-NMR and ATR-FTIR. Studies in dilute aqueous media by dynamic and electrophoretic light scattering (DLS and ELS) show their potential responsiveness regarding changes in temperature, pH, and kosmotropic salt concentration. Finally, the change in hydrophilic/hydrophobic balance of the formed terpolymer nanoparticles during heating and cooling was studied using fluorescence spectroscopy (FS) in conjunction with pyrene giving additional information on the responsiveness and internal structure of the self-assembled nanoaggregates.