Synthesis and Study of Thermoresponsive Amphiphilic Copolymers via RAFT Polymerization

Synthesis and study of well-defined thermoresponsive amphiphilic copolymers with various compositions were reported. Kinetics of the reversible addition-fragmentation chain transfer (RAFT) (co)polymerization of styrene (St) and oligo(ethylene glycol) methyl ether methacrylate (PEO5MEMA) was studied by size exclusion chromatography (SEC) and 1H NMR spectroscopy, which allows calculating not only (co)polymerization parameters but also gives valuable information on RAFT (co)polymerization kinetics, process control, and chain propagation. Molecular weight Mn and dispersity Đ of the copolymers were determined by SEC with triple detection. The detailed investigation of styrene and PEO5MEMA (co)polymerization showed that both monomers prefer cross-polymerization due to their low reactivity ratios (r1 < 1, r2 < 1); therefore, the distribution of monomeric units across the copolymer chain of p(St-co-PEO5MEMA) with various compositions is almost ideally statistical or azeotropic. The thermoresponsive properties of p(St-co-PEO5MEMA) copolymers in aqueous solutions as a function of different hydrophilic/hydrophobic substituent ratios were evaluated by measuring the changes in hydrodynamic parameters under applied temperature using the dynamic light scattering method (DLS).

Dextran-Coated Latex Nanoparticles via Photo-RAFT Mediated Polymerization Induced Self-Assembly

Polysaccharide coated nanoparticles represent a promising class of environmentally friendly latex to replace those stabilized by small toxic molecular surfactants. We report here an in situ formulation of free-surfactant core/shell nanoparticles latex consisting of dextran-based diblock amphiphilic copolymers. The synthesis of copolymers and the immediate latex formulation were performed directly in water using a photo-initiated reversible addition fragmentation chain transfer-mediated polymerization induced self-assembly strategy. A hydrophilic macromolecular chain transfer-bearing photosensitive thiocarbonylthio group (eDexCTA) was first prepared by a modification of the reducing chain end of dextran in two steps: (i) reductive amination by ethylenediamine in the presence of sodium cyanoborohydride, (ii) then introduction of CTA by amidation reaction. Latex nanoparticles were then formulated in situ by chain-extending eDexCTA using 2-hydroxypropyl methacrylate (HPMA) under 365 nm irradiation, leading to amphiphilic dextran-b-poly(2-hydroxypropyl methacrylate) diblock copolymers (DHX). Solid concentration (SC) and the average degree of polymerization - Xnˉ- of PHPMA block (X) were varied to investigate their impact on the size and the morphology of latex nanoparticles termed here SCDHX. Light scattering and transmission electron microscopy analysis revealed that SCDHX form exclusively spherical nano-objects. However, the size of nano-objects, ranging from 20 nm to 240 nm, increases according to PHPMA block length.

Selective solvent conditions influence sequence development and supramolecular assembly in step-growth copolymerization

Sequence control in synthetic copolymers remains a tantalizing objective in polymer science due to the influence of sequence on material properties and self-organization. A greater understanding of sequence development throughout the polymerization process will aid the design of simple, generalizable methods to control sequence and tune supramolecular assembly. In previous simulations of solution-based step-growth copolymerizations, we have shown that weak, non-bonding attractions between monomers of the same type can produce a microphase separation among the lengthening nascent oligomers and thereby alter sequence. This work explores the phenomenon further, examining how effective attractive interactions, mediated by a solvent selective for one of the reacting species, impact the development of sequence and the supramolecular assembly in a simple A-B copolymerization. We find that as the effective attractions between monomers increase, an emergent self-organization of the reactants causes a shift in reaction kinetics and sequence development. When the solvent-mediated interactions are selective enough, the simple mixture of A and B monomers oligomerize and self-assemble into structures characteristic of amphiphilic copolymers. The composition and morphology of these structures and the sequences of their chains are sensitive to the relative balance of affinities between the comonomer species. Our results demonstrate the impact of differing A-B monomer-solvent affinities on sequence development in solution-based copolymerizations and are of consequence to the informed design of synthetic methods for sequence controlled amphiphilic copolymers and their aggregates.

Development of poly(ethyleneimine) grafted amphiphilic copolymers: Evaluation of their cytotoxicity and ability to complex DNA

Poly(ethyleneimine) (PEI) is one of the most widely used cationic polymers for gene delivery. The high molecular weight polymer, which is commercially available, is highly efficient but also very cytotoxic. The reduction in charge density by using nonlinear architectures based on low molecular weight (LMW) PEI is a promising approach to produce safer DNA-vectors. Herein, a group of cationic graft copolymers with different composition containing a hydrophobic biocompatible backbone and LMW linear PEI (lPEI) grafts obtained by ring opening polymerization and click chemistry was studied. The self-assembly and DNA complexation behavior of these materials was analyzed by the gel retardation assay, zeta potential measurements, and dynamic light scattering. The copolymers formed positively charged particles in water with average sizes between 270 and 377 nm. After they were added to DNA in serum-free medium, these particles acquired negative/near-neutral charges and increased in size depending on the N/P ratio. All copolymers showed reduced cytotoxicity compared to the 25 kDa lPEI used as reference, but the transfection efficiency was reduced. This result suggested that the cationic segments were too small to fully condense the DNA and promote cellular uptake, even with the use of several grafts and the introduction of hydrophobic domains. The trends found in this research showed that a higher degree of hydrophobicity and a higher grafting density can enhance the interaction between the copolymers and DNA. These trends could direct further structural modifications in the search for effective and safe vectors based on this polycation.

Hydrogels Classification According to the Physical or Chemical Interactions and as Stimuli-Sensitive Materials

Hydrogels are attractive biomaterials with favorable characteristics due to their water uptake capacity. However, hydrogel properties are determined by the cross-linking degree and nature, the tacticity, and the crystallinity of the polymer. These biomaterials can be sorted out according to the internal structure and by their response to external factors. In this case, the internal interaction can be reversible when the internal chains are led by physicochemical interactions. These physical hydrogels can be synthesized through several techniques such as crystallization, amphiphilic copolymers, charge interactions, hydrogen bonds, stereo-complexing, and protein interactions. In contrast, the internal interaction can be irreversible through covalent cross-linking. Synthesized hydrogels by chemical interactions present a high cross-linking density and are employed using graft copolymerization, reactive functional groups, and enzymatic methods. Moreover, specific smart hydrogels have also been denoted by their external response, pH, temperature, electric, light, and enzyme. This review deeply details the type of hydrogel, either the internal structure or the external response. Furthermore, we detail some of the main applications of these hydrogels in the biomedicine field, such as drug delivery systems, scaffolds for tissue engineering, actuators, biosensors, and many other applications.

Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-deoxy-2-methacrylamido-d-glucose)/Poly(N-vinyl succinamic acid) with Poly(O-cholesteryl methacrylate) for Delivery of Hydrophobic Drugs

The self-assembly of amphiphilic block-copolymers is a convenient way to obtain soft nanomaterials of different morphology and scale. In turn, the use of a biomimetic approach makes it possible to synthesize polymers with fragments similar to natural macromolecules but more resistant to biodegradation. In this study, we synthesized the novel bio-inspired amphiphilic block-copolymers consisting of poly(N-methacrylamido-d-glucose) or poly(N-vinyl succinamic acid) as a hydrophilic fragment and poly(O-cholesteryl methacrylate) as a hydrophobic fragment. Block-copolymers were synthesized by radical addition–fragmentation chain-transfer (RAFT) polymerization using dithiobenzoate or trithiocarbonate chain-transfer agent depending on the first monomer, further forming the hydrophilic block. Both homopolymers and copolymers were characterized by 1H NMR and Fourier transform infrared spectroscopy, as well as thermogravimetric analysis. The obtained copolymers had low dispersity (1.05–1.37) and molecular weights in the range of ~13,000–32,000. The amphiphilic copolymers demonstrated enhanced thermal stability in comparison with hydrophilic precursors. According to dynamic light scattering and nanoparticle tracking analysis, the obtained amphiphilic copolymers were able to self-assemble in aqueous media into nanoparticles with a hydrodynamic diameter of approximately 200 nm. An investigation of nanoparticles by transmission electron microscopy revealed their spherical shape. The obtained nanoparticles did not demonstrate cytotoxicity against human embryonic kidney (HEK293) and bronchial epithelial (BEAS-2B) cells, and they were characterized by a low uptake by macrophages in vitro. Paclitaxel loaded into the developed polymer nanoparticles retained biological activity against lung adenocarcinoma epithelial cells (A549).

Upconversion Nanoparticles Encapsulated with Molecularly Imprinted Amphiphilic Copolymer as a Fluorescent Probe for Specific Biorecognition

A fluorescent probe for specific biorecognition was prepared by a facile method in which amphiphilic random copolymers were encapsulated with hydrophobic upconversion nanoparticles (UCNPs). This method quickly converted the hydrophobic UCNPs to hydrophilic UNCPs. Moreover, the self-folding ability of the amphiphilic copolymers allowed the formation of molecular imprinting polymers with template-shaped cavities. LiYF4:Yb3+/Tm3+@LiYF4:Yb3+ UCNP with up-conversion emission in the visible light region was prepared; this step was followed by the synthesis of an amphiphilic random copolymer, poly(methacrylate acid-co-octadecene) (poly(MAA-co-OD)). Combining the UCNPs and poly(MAA-co-OD) with the templates afforded a micelle-like structure. After removing the templates, UCNPs encapsulated with the molecularly imprinted polymer (MIP) (UCNPs@MIP) were obtained. The adsorption capacities of UCNPs@MIP bound with albumin and hemoglobin, respectively, were compared. The results showed that albumin was more easily bound to UCNPs@MIP than to hemoglobin because of the effect of protein conformation. The feasibility of using UCNPs@MIP as a fluorescent probe was also studied. The results showed that the fluorescence was quenched when hemoglobin was adsorbed on UCNPs@MIP; however, this was not observed for albumin. This fluorescence quenching is attributed to Förster resonance energy transfer (FRET) and overlap of the absorption spectrum of hemoglobin with the fluorescence spectrum of UCNPs@MIP. To our knowledge, the encapsulation approach for fabricating the UCNPs@MIP nanocomposite, which was further used as a fluorescent probe, might be the first report on specific biorecognition.