Idriss Blakey

Functional hyperbranched polymers: toward targeted in vivo 19F magnetic resonance imaging using designed macromolecules.

We have demonstrated the design and synthesis of hyperbranched molecules that can be successfully imaged in vivo using (19)F MRI in under 10 min. These polymers are cytocompatible following chain extension with PEGMA. In addition, functionalization of these macromolecules can be achieved in a facile manner and with accessible and correct ligand presentation. Such hyperbranched polymers hold promise as new generation tracking and targeting MRI contrast agents.

Multimodal Polymer Nanoparticles with Combined 19F Magnetic Resonance and Optical Detection for Tunable, Targeted, Multimodal Imaging in Vivo

Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution (19)F/(1)H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.

Raman spectral mapping of photo-oxidised polypropylene

Raman spectral mapping at a microscopic scale has been used to probe the heterogeneous photo-oxidation of unstabilised single particles and films of polypropylene (PP). Analysis of resonance Raman spectra in conjunction with SEM/EDX data allowed determination of the distribution of polymerisation catalyst residues throughout the polymer. However, the distribution of oxidation products was found not to correlate with the distribution of catalyst. Consequently, a conclusion was drawn that the catalyst residues, for the type of PP studied, tend to stabilise the polymer in the immediate vicinity, but also form reactive species that diffuse away from the catalyst to initiate oxidation (C) 2000 Elsevier Science Ltd. All rights reserved.

Molecular imaging with polymers

Polymers open up new possibilities in the field of molecular imaging, allowing sensitive and robust agents that can be imaged over long periods of time. This review highlights some recent advances in polymeric molecular imaging agents in both (pre)clinical and emerging applications.

Control of the orientation of symmetric poly(styrene)-block-poly(D,L-lactide) block copolymers using statistical copolymers of dissimilar composition

The interactions of block copolymers with surfaces can be controlled by coating those surfaces with appropriate statistical copolymers. Usually, a statistical copolymer comprised of monomer units identical to those of the block copolymer is used; that is, typically a poly(styrene)-stat-poly(methyl methacrylate) (PS-stat-PMMA) is used to direct the alignment of poly(styrene)-block-poly(methyl methacrylate) (PS-block-PMMA), and poly(styrene)-stat-poly(2-vinylpyridine) (PS-stat-P2VP) has been used for poly(styrene)-block-poly(2-vinylpyridine) (PS-block-P2VP). Reports of controlling the orientation of block copolymers with statistical copolymers with a dissimilar composition are limited. Here, we demonstrate that this method can be further extended to show that PS-stat-PMMA can be used to control the wetting properties of poly(styrene)-block-poly(D,L-lactide) (PS-block-PDLA). Surfaces were modified with a series of cross-linked PS-stat-PMMA-stat-glycidyl methacrylate terpolymers, and the surface chemistries and energies were assessed using angle-dependent X-ray photoelectron spectroscopy and the two-liquid harmonic method, respectively. From these experiments, an expected neutral compositional window was identified for symmetrical PS-block-PDLA. Moreover, high-resolution SEM, AD-XPS, and grazing-incidence SAXS measurements were used to evaluate the morphology of PS-block-PDLA as a function of the surface composition of the underlying cross-linked copolymer films, and the neutral composition was found to range from 32 to 38 mol % of PS, in the bulk polymer. Ultimately, we demonstrated the determination of nonpreferential surface compositions that allow the self-assembly of lamellae with sizes in the sub-10 nm regime that are oriented perpendicular to the substrate. These findings have important implications for the use of PS-block-PDLA block copolymers in directed self-assembly, most specifically in advanced lithographic processes.

A Method for Controlling the Aggregation of Gold Nanoparticles: Tuning of Optical and Spectroscopic Properties

Gold nanoparticles (AuNPs) have many interesting optical properties, which are derived from their surface plasmon resonance (SPR). However, the SPR of single AuNPs occurs around 520 nm, which is a limitation for biomedical imaging applications, because the maximum falls outside the tissue transparency window (∼650-1000 nm). Here the aggregation of AuNPs is mediated by balancing aggregation and steric stabilization processes. This is achieved by varying the relative amounts of hydrophobic small molecules, which act as aggregating agents, and end functional hydrophilic polymers that serve as steric stabilizing agents. This approach allows the position of the SPR shifted into the tissue transparency window, while maintaining colloidal stability. Importantly, increased depolarized scattering and surface enhanced Raman scattering (SERS) cross sections in this region are achieved compared to the single nanoparticles. By varying the structure of the aggregating agent slightly, the SERS spectra exhibit significant changes, thus demonstrating the potential to encode different aggregates. The aggregates have potential applications in biomedical imaging, as an encoding strategy for combinatorial chemistry, and for use in flow cytometry applications.

Self assembly of plasmonic core–satellite nano-assemblies mediated by hyperbranched polymer linkers

The morphology of plasmonic nano-assemblies has a direct influence on optical properties, such as localised surface plasmon resonance (LSPR) and surface enhanced Raman scattering (SERS) intensity. Assemblies with core-satellite morphologies are of particular interest, because this morphology has a high density of hot-spots, while constraining the overall size. Herein, a simple method is reported for the self-assembly of gold NPs nano-assemblies with a core-satellite morphology, which was mediated by hyperbranched polymer (HBP) linkers. The HBP linkers have repeat units that do not interact strongly with gold NPs, but have multiple end-groups that specifically interact with the gold NPs and act as anchoring points resulting in nano-assemblies with a large (∼48 nm) core surrounded by smaller (∼15 nm) satellites. It was possible to control the number of satellites in an assembly which allowed optical parameters such as SPR maxima and the SERS intensity to be tuned. These results were found to be consistent with finite-difference time domain (FDTD) simulations. Furthermore, the multiplexing of the nano-assemblies with a series of Raman tag molecules was demonstrated, without an observable signal arising from the HBP linker after tagging. Such plasmonic nano-assemblies could potentially serve as efficient SERS based diagnostics or biomedical imaging agents in nanomedicine.

Controlled polymerisation of lactide using an organo-catalyst in supercritical carbon dioxide

The controlled, ring-opening polymerisation of DL-lactide in supercritical carbon dioxide (scCO2) using benzyl alcohol as an initiator and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an organo-catalyst, is reported. Despite reports of DBU being efficiently converted to a carbonate salt in the presence of a proton source, it was found that DBU was still an efficient catalyst for the ring opening polymerisation of DL-lactide. Matrix-assisted laser desorption ionisation time of flight mass spectroscopy and 1H nuclear magnetic resonance analysis demonstrated that end-group fidelity was maintained on the resulting polymer and significant transesterification was not observed under anhydrous conditions. We report a truly ‘green’ process for the synthesis of polylactic acid (PLA) with the total absence of potentially toxic organic solvents and inorganic catalysts. In addition, the reaction in scCO2 is conducted at temperatures much lower than that required for bulk polymerisation of LA.

Interactions of Phenyldithioesters with Gold Nanoparticles (AuNPs): Implications for AuNP Functionalization and Molecular Barcoding of AuNP Assemblies

The interactions of phenyldithioesters with gold nanoparticles (AuNPs) have been studied by monitoring changes in the surface plasmon resonance (SPR), depolarised light scattering, and surface enhanced Raman spectroscopy (SERS). Changes in the SPR indicated that an AuNP-phenyldithioester charge transfer complex forms in equilibrium with free AuNPs and phenyldithioester. Analysis of the Langmuir binding isotherms indicated that the equilibrium adsorption constant, K(ads), was 2.3 +/- 0.1 x 10(6) M(-1), which corresponded to a free energy of adsorption of 36 +/- 1 kJ mol(-1). These values are comparable to those reported for interactions of aryl thiols with gold and are of a similar order of magnitude to moderate hydrogen bonding interactions. This has significant implications in the application of phenyldithioesters for the functionalization of AuNPs. The SERS results indicated that the phenyldithioesters interact with AuNPs through the C=S bond, and the molecules do not disassociate upon adsorption to the AuNPs. The SERS spectra are dominated by the portions of the molecule that dominate the charge transfer complex with the AuNPs. The significance of this in relation to the use of phenyldithioesters for molecular barcoding of nanoparticle assemblies is discussed.

Hyperbranched Polymer–Gold Nanoparticle Assemblies: Role of Polymer Architecture in Hybrid Assembly Formation and SERS Activity

Plasmonic gold nanoassemblies that self-assemble with the aid of linking molecules or polymers have the potential to yield controlled hierarchies of morphologies and consequently result in materials with tailored optical (e.g., localized surface plasmon resonances (LSPR)) and spectroscopic properties (e.g., surface-enhanced Raman scattering (SERS)). Molecular linkers that are structurally well-defined are promising for forming hybrid nanoassemblies which are stable in aqueous solution and are increasingly finding application in nanomedicine. Despite much ongoing research in this field, the precise role of molecular linkers in governing the morphology and properties of the hybrid nanoassemblies remains unclear. Previously we have demonstrated that branched linkers, such as hyperbranched polymers, with specific anchoring end groups can be successfully employed to form assemblies of gold NPs demonstrating near-infrared SPRs and intense SERS scattering. We herein introduce a tailored polymer as a versatile molecular linker, capable of manipulating nanoassembly morphologies and hot-spot density. In addition, this report explores the role of the polymeric linker architecture, specifically the degree of branching of the tailored polymer in determining the formation, morphology, and properties of the hybrid nanoassemblies. The degree of branching of the linker polymer, in addition to the concentration and number of anchoring groups, is observed to strongly influence the self-assembly process. The assembly morphology shifts primarily from 1D-like chains to 2D plates and finally to 3D-like globular structures, with increase in degree of branching of the macromolecular linker. Insights have been gained into how the morphology influences the SERS performance of these nanoassemblies with respect to hot-spot density. These findings supplement the understanding of the morphology determining nanoassembly formation and pave the way for the possible application of these nanoassemblies as SERS biosensors for medical diagnostics.