Theoni K. Georgiou

Polymeric theranostics: using polymer-based systems for simultaneous imaging and therapy

Polymer-based nanomedicine is a large and fast growing field. Polymer-based systems have been extensively used as therapeutic carriers as well as bioimaging agents for example in tumour diagnosis. However, fewer polymeric systems have been able to combine both therapy and imaging in a new field that is called theranostics (theragnostics). This review aims to summarise the recent developments and trends on polymeric theranostics. Four different types of therapies/treatments are examined namely drug delivery, gene delivery, photodynamic therapy and hyperthermia treatment combined with different imaging moieties like magnetic resonance imaging agents, fluorescent agents and microbubbles for ultrasound imaging.

Synthesis, Characterization, and DNA Adsorption Studies of Ampholytic Model Conetworks Based on Cross-Linked Star Copolymers

Five model conetworks based on cross-linked star ampholytic copolymers were synthesized by group transfer polymerization. The ampholytic copolymers were based on two hydrophilic monomers: the positively ionizable 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the negatively ionizable methacrylic acid (MAA). Ethylene glycol dimethacrylate was used as the cross-linker. These five ampholytic model conetworks were isomers based on equimolar DMAEMA-MAA copolymer stars of different architectures: heteroarm (two), star block (two), and statistical. The two networks based on the homopolymer stars were also synthesized. The MAA units were introduced via the polymerization of tetrahydropyranyl methacrylate and the acid hydrolysis of the latter after network formation. All the precursors to the (co)networks were characterized in terms of their molecular weights using gel permeation chromatography (GPC). The mass of the extractables from the (co)networks was measured and characterized in terms of molecular weight and composition using GPC and proton nuclear magnetic resonance (1H NMR) spectroscopy, respectively. The degrees of swelling (DS) of all the ampholytic conetworks were measured as a function of pH and were found to present a minimum at a pH value which was taken as the isoelectric point, pI. The DS and the pI values did not present a dependence on conetwork architecture. Finally, DNA adsorption studies onto the ampholyte conetworks indicated that DNA binding was governed by electrostatics.

Thermoresponsive triblock copolymers based on methacrylate monomers: effect of molecular weight and composition

A series of amphiphilic thermoresponsive ABC triblock copolymers was synthesised by Group Transfer Polymerisation (GTP). In total nine polymers were prepared based on the non-ionic hydrophobic n-butyl methacrylate (BuMA), the ionisable hydrophilic and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the non-ionic hydrophilic methoxy poly(ethylene glycol) methacrylate (PEGMA). The architecture of the copolymers was kept constant with the hydrophobic block in the middle and the two hydrophilic blocks at the two ends, while the composition and the molecular weight of the polymers were varied. Specifically the molecular weight of the polymers was varied while the composition and the architecture were kept constant. The precursors to the polymers and the polymers were characterised in terms of their molecular weight and composition using gel permeation chromatography and proton nuclear magnetic resonance spectroscopy, respectively. Aqueous solutions of the polymers were studied by turbidimetry, hydrogen ion titration and light scattering to determine their cloud points, pKas, and hydrodynamic diameters and investigate the effect of the composition and the molecular weight of the copolymers. Finally, the thermoresponsive behaviour of the copolymers was also studied and it was found that the cloud point and gel point of the polymers were strongly affected by both the composition and molecular weight of the triblock copolymers.

Multicompartment thermoresponsive gels: does the length of the hydrophobic side group matter?

Multicompartment thermoresponsive gels are novel materials with fascinating self-assembly and interesting applications. The aim of this study was to investigate for the first time the effect of the length of the alkyl side group of a hydrophobic monomer on the thermoresponsive and self-assembly behaviour of terpolymers. Specifically twelve well-defined terpolymers based on the hydrophilic monomers 2-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA), and on the hydrophobic monomer ethyl-, n-butyl or n-hexyl methacrylate (EtMA, BuMA or HMA) of varying architectures (ABC, ACB, BAC and statistical) were synthesised using Group Transfer Polymerisation. The A, B and C blocks were based on PEGMA, the alkyl containing methacrylate monomer, and DMAEMA, respectively. The molecular weights (MWs) and compositions of the polymers were kept the same. The polymers and their precursors were characterised in terms of their MWs, MW distributions and compositions. Aqueous solutions of the polymers were studied by turbidimetry, hydrogen ion titration, light scattering and rheology to determine their cloud points, pKas, hydrodynamic diameters and thermoresponsive behaviour and investigate the effect of the architecture and the hydrophobic alkyl side group of the terpolymers. It was found that the pKas and the Tgs were mostly affected by the hydrophobicity of the side groups and not by the architecture, while the cloud points and the sol–gel transition of the polymers were affected by both the length of the alkyl side group and the polymer architecture. Interestingly the sharpest sol–gel transitions and stable multicompartment hydrogels were observed for the ABC triblock copolymers with the short alkyl-side groups even though the sol–gel transition occurred at higher temperatures.

Autonomous self-healing structural composites with bio-inspired design

Strong and tough natural composites such as bone, silk or nacre are often built from stiff blocks bound together using thin interfacial soft layers that can also provide sacrificial bonds for self-repair. Here we show that it is possible exploit this design in order to create self-healing structural composites by using thin supramolecular polymer interfaces between ceramic blocks. We have built model brick-and-mortar structures with ceramic contents above 95 vol% that exhibit strengths of the order of MPa (three orders of magnitude higher than the interfacial polymer) and fracture energies that are two orders of magnitude higher than those of the glass bricks. More importantly, these properties can be fully recovered after fracture without using external stimuli or delivering healing agents. This approach demonstrates a very promising route towards the design of strong, ideal self-healing materials able to self-repair repeatedly without degradation or external stimuli.

Thermoresponsive gels based on ABC triblock copolymers: effect of the length of the PEG side group

In this study, one statistical and nine well-defined ABC triblock thermoresponsive terpolymers were synthesised via group transfer polymerisation (GTP). The A, B, and C blocks were based on poly(ethylene glycol) (PEG) based methacrylate, n-butyl methacrylate (BuMA), and 2-(dimethylamino)ethyl methacrylate (DMAEMA), respectively. The length of the PEG side group was varied. Specifically, three different PEG based monomers were used: methoxy di-, penta-, and nona(ethylene glycol) methacrylate (DEGMA, PEGMA, and NEGMA, respectively). Along with the length of the PEG side group, the composition of the terpolymers was also systematically varied in order to investigate the effect of both these parameters on the thermoresponsive behaviour of the polymers. The molar mass (MM) and the architecture were kept the same. Their hydrodynamic diameters, the effective pKas, and the cloud points of aqueous copolymer solutions were determined by dynamic light scattering (DLS), potentiometric titrations, and visual tests, respectively. Micelle formation was observed for all the copolymers and the pKas were influenced by the hydrophobic content but not by the PEG side length. On the other hand both the composition and the PEG side chain length affected the cloud points and the sol–gel transition. In summary, it was demonstrated that the sol–gel transition can be tailored by varying both the PEG length as well as the composition of the polymers.

ABC triblock copolymer micelles: Spherical versus worm-like micelles depending on the preparation method

Well-defined ABC triblock copolymers based on two hydrophilic blocks, A and C, and a hydrophobic block B are synthesized and their self-assembly behavior is investigated. Interestingly, at the same solvent, concentration, pH, and temperature, different shape micelles are observed, spherical and worm-like micelles, depending on the preparation method. Specifically, spherical micelles are observed with bulk rehydration while both spherical and worm-like micelles are observed with film rehydration.

Tailoring pH-responsive acrylic acid microgels with hydrophobic crosslinks for drug release

Amphiphilic microgels based on the hydrophilic acrylic acid (AA) and hydrophobic crosslinks of different compositions were synthesised using a lab-on-a-chip device. The microgels were formed by polymerising hydrophobic droplets. The droplets were generated via a microfluidic platform and contained a protected form of AA, a hydrophobic crosslinker (ethylene glycol dimethacrylate, EGDMA) and a free radical initiator in an organic solvent. Following photopolymerisation and subsequent hydrolysis, AA based microgels of amphiphilic nature were produced and it was demonstrated that they can successfully deliver both hydrophilic as well as hydrophobic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the aqueous solution as well as the crosslinking density and hydrophobic content of the microgels.

Novel “core-first” star-based quasi-model amphiphilic polymer networks

Novel quasi-model networks based on “core-first” star (co)polymers have been synthesised. The polymeric networks (gels) were based on the hydrophilic, thermo- and pH-responsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the non-ionic, hydrophobic methyl methacrylate (MMA). Specifically two homopolymer networks and three amphiphilic polymer networks were synthesised based on two block and one statistical “core-first” star copolymers. The precursors to and the extractables of the networks were characterised using Gel Permeation Chromatography and proton Nuclear Magnetic Resonance to determine the molecular weight, polydispersity and composition. The degrees of swelling (DSs) of the networks were then determined in both aqueous and organic solvents. The DSs in organic solvents and non-acidic water were dependant only on the composition of the conetworks while the DSs in acidic water were also affected by the architecture of the conetworks. Finally the networks were evaluated in terms of their ability to absorb and deliver hydrophilic and hydrophobic compounds that were used as “model drugs” and interestingly it was observed that the architecture of the networks, and not just the composition of the networks, affected the release of the compounds.

Toward Hybrid Materials: Group Transfer Polymerization of 3-(Trimethoxysilyl)propyl Methacrylate.

In this study, the group transfer polymerization (GTP) of the functional monomer 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) is reported to produce polymers of different architectures and topologies. TMSPMA is successfully polymerized and copolymerized with GTP to produce well-defined (co)polymers that can be used to fabricate functional hybrid materials like hydrogels and films.