This review aims to highlight the most recent advances in the field of the synthesis of branched copolymers and nanogels using reversible addition-fragmentation chain transfer (RAFT) polymerization. RAFT polymerization is a reversible deactivation radical polymerization technique (RDRP) that has gained tremendous attention due to its versatility, compatibility with a plethora of functional monomers, and mild polymerization conditions. These parameters lead to final polymers with good control over the molar mass and narrow molar mass distributions. Branched polymers can be defined as the incorporation of secondary polymer chains to a primary backbone, resulting in a wide range of complex macromolecular architectures, like star-shaped, graft, and hyperbranched polymers and nanogels. These subcategories will be discussed in detail in this review in terms of synthesis routes and properties, mainly in solutions.

Mixed micelles from copolymers in aqueous media have emerged as a valuable tool for producing functional polymer nanostructures with applications in nanomedicine, including drug delivery and bioimaging. In this review, we discuss the basics of mixed copolymer micelles’ design, structure, and physicochemical properties. We also focus on their utilization in biomedical applications using examples from recent literature.

The synthesis of novel copolymers using one-step reversible addition-fragmentation chain transfer (RAFT) copolymerization of biocompatible methacrylic acid (MAA), lauryl methacrylate (LMA), and difunctional ethylene glycol dimethacrylate (EGDMA) as a branching agent is reported. The obtained amphiphilic hyperbranched H-P(MAA-co-LMA) copolymers are molecularly characterized by size exclusion chromatography (SEC), FTIR, and ¹H-NMR spectroscopy, and subsequently investigated in terms of their self-assembly behavior in aqueous media. The formation of nanoaggregates of varying size, mass, and homogeneity, depending on the copolymer composition and solution conditions such as concentration or pH variation, is demonstrated by light scattering and spectroscopic techniques. Furthermore, drug encapsulation properties are studied by incorporating the low bioavailability drug, curcumin, in the nano-aggregate hydrophobic domains, which can also act as a bioimaging agent. The interaction of polyelectrolyte MAA units with model proteins is described to examine protein complexation capacity relevant to enzyme immobilization strategies, as well as explore copolymer self-assembly in simulated physiological media. The results confirm that these copolymer nanosystems could provide competent biocarriers for imaging and drug or protein delivery/enzyme immobilization applications.

In this study, reversible addition-fragmentation chain transfer (RAFT) polymerization is utilized in order to synthesize novel hyperbranched poly(oligoethylene glycol) methyl ether methacrylate-co-tert-butyl methacrylate-co-methacrylic acid) (H-[P(OEGMA-co-tBMA-co-MAA)]) copolymers in combination with selective hydrolysis reactions. The copolymers showing amphiphilicity induced by the polar OEGMA and hydrophobic tBMA monomeric units, and polyelectrolyte character due to MAA units, combined with unique macromolecular architecture were characterized by physicochemical techniques, such as size exclusion chromatography (SEC) and ¹H-NMR spectroscopy. The hyperbranched copolymers were investigated in terms of their ability to self-assemble into nanostructures when dissolved in aqueous media. Dynamic light scattering and fluorescence spectroscopy revealed multimolecular aggregates of nanoscale dimensions with low critical aggregation concentration, the size and mass of which depend on copolymer composition and solution conditions, whereas zeta potential measurements indicated pH sensitive features. In addition, aiming to evaluate their potential use as nanocarriers, the copolymers were studied in terms of their drug encapsulation and protein complexation ability utilizing curcumin and lysozyme, as a model hydrophobic drug and a model cationic protein, respectively.

This manuscript presents the synthesis of hyperbranched amphiphilic poly (lauryl methacrylate-co-tert-butyl methacrylate-co-methacrylic acid), H-P(LMA-co-tBMA-co-MAA) copolymers via reversible addition fragmentation chain transfer (RAFT) copolymerization of tBMA and LMA, and their post-polymerization modification to anionic amphiphilic polyelectrolytes. The focus is on investigating whether the combination of the hydrophobic characters of LMA and tBMA segments, as well as the polyelectrolyte and hydrophilic properties of MAA segments, both distributed within a unique hyperbranched polymer chain topology, would result in intriguing, branched copolymers with the potential to be applied in nanomedicine. Therefore, we studied the self-assembly behavior of these copolymers in aqueous media, as well as their ability to form complexes with cationic proteins, namely lysozyme (LYZ) and polymyxin (PMX). Various physicochemical characterization techniques, including size exclusion chromatography (SEC) and proton nuclear magnetic resonance (¹H-NMR), verified the molecular characteristics of these well-defined copolymers, whereas light scattering and fluorescence spectroscopy techniques revealed promising nanoparticle (NP) self- and co-assembly properties of the copolymers in aqueous media.

In this study, we explore the design of novel random poly(lauryl methacrylate-co-tert-butyl methacrylate-co-methacrylic acid), P(LMA-co-tBMA-co-MAA) copolymers via the RAFT copolymerization of LMA and tBMA followed by the selective hydrolysis of tBMA segments. For the molecular characterization of the novel copolymer, a series of physicochemical techniques were implemented, including size exclusion chromatography (SEC), proton nuclear magnetic resonance (¹H-NMR) and attenuated total reflectance–Fourier transform infrared (ATR–FTIR) spectroscopy. Our experimental results confirmed the successful synthesis of the targeted copolymers. The compositions were in accordance with the targeted differing fraction of hydrophobic tBMA/LMA elements, and hydrolysis resulted in at least 64% conversion to hydrophilic MAA units. The copolymers, bearing both an amphiphilic character and polyelectrolyte properties while being composed of randomly distributed monomeric segments of biocompatible materials, were subsequently investigated in terms of their self-assembly behavior in aqueous solutions. Dynamic light scattering and fluorescence spectroscopy experiments demonstrated the formation of self-assembled nanoaggregates (average hydrodynamic radii, R_h < 100 nm) that formed spontaneously, having low critical aggregation concentration (CAC) values (below 3.5 × 10⁻⁶ g/mL), and highlighted the feasibility of using these copolymer systems as nanocarriers for biomedical applications.