[Show abstract][Hide abstract] ABSTRACT: Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early-stage cancer diagnosis. Gadolinium (Gd) (III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high x-ray attenuation coefficient, is an ideal contrast agent candidate for x-ray based CT imaging. Gd metal organic framework (MOF) nanoparticles with tunable size, high Gd (III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multi-modal imaging probes.
[Show abstract][Hide abstract] ABSTRACT: Functional imaging is a novel area in radiological sciences and allows for the non-invasive assessment and visualization of specific targets such as gene and protein expression, metabolic rates, and drug delivery in intact living subjects. As such, the field of molecular imaging has been defined as the non-invasive, quantitative, and repetitive imaging of biomolecules and biological processes in living organisms. For example, cancer cells may be genetically altered to attract molecules that alter the magnetic susceptibility, thereby permitting their identification by magnetic resonance imaging. These contrast agents and/or molecular reporters are seen as essential to the task of molecular medicine to increase both sensitivity and specificity of imaging. Therefore, there are five general principles which need to be fulfilled in order to conduct a successful in vivo molecular imaging study: (1) selection of appropriate cellular and subcellular targets; (2) development of suitable in vivo affinity ligands (molecular probes); (3) delivery of these probes to the target organ; (4) amplification strategies able to detect minimal target concentrations; and (5) development of imaging systems with high resolution. Although there has been a wide range of routes taken to incorporate both imaging agents and a disease-targeting moiety into diagnostic devices, arguably the most interesting of these routes employs the use of nanoparticles. Nanoscale diagnostic systems that incorporate molecular targeting agents and diagnostic imaging capabilities are emerging as the next-generation imaging agents and have the potential to dramatically improve the outcome of the imaging, diagnosis, and treatment of a wide range of diseases. The present review addresses chemical aspects in development of molecular probes based upon gadolinium nanoparticles and their potential role in translational clinical imaging and therapy.
[Show abstract][Hide abstract] ABSTRACT: A novel surface modification technique was employed to produce a polymer-modified, positive contrast agent nanoparticle for targeted magnetic resonance imaging (MRI). A range of both hydrophilic and hydrophobic homopolymers, along with novel multifunctional copolymers of poly(N-(2-hydroxypropyl) methacrylamide)-co-poly(N-methacryloxysuccinimide)-co-poly(fluorescein O-methacrylate), were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. These polymers were subsequently used to modify the surface of gadolinium (Gd) metal-organic framework (MOF) nanoparticles. The succinimide functionality of the copolymer was utilized as a scaffold for attachment of the targeting ligands, H-glycine-arginine-glycine-aspartate-serine-NH2 peptide or the antibody for epidermal growth factor. Reduction of the trithiocarbonate RAFT polymer end groups to thiolates provided a means of polymer attachment through vacant orbitals on the Gd3+ ions at the surface of the Gd MOF nanoparticles. MRI confirmed that the relaxivity rates of these novel polymer-modified structures were easily tuned by changes in size and shape of the nanoparticles or by modifying the molecular weight and chemical structure of the polymers attached to the surface of the nanoparticles. In most cases, the relaxivity values were significantly higher than both the unmodified Gd MOF nanoparticles and the clinically employed contrast agents, Magnevist® and MultiHance®. These versatile, polymer-modified nanoscale scaffolds were shown to provide biocompatibility, cancer cell targeting, and diagnostic imaging through positive contrast in MRI and fluorescence microscopy. This unique method provided a simple yet versatile route of producing polymer-modified nanoparticles for targeted MRI of cancer with an unprecedented degree of flexibility in the construct, potentially allowing for tunable loading capacities and spatial loading of targeting agents while incorporating bimodal imaging capabilities.
Multifunctional Nanoparticles for Drug Delivery Applications, 01/2012: pages 173-198;
[Show abstract][Hide abstract] ABSTRACT: Gadolinium metal-organic framework (Gd MOF) nanoparticles are an interesting and novel class of nanomaterials that are being studied as a potential replacement for small molecule positive contrast agents in magnetic resonance imaging (MRI). Despite the tremendous interest in these nanoscale imaging constructs, there are limitations, particularly with respect to controlling the particle size, which need to be overcome before these nanoparticles can be integrated into in vivo applications. In an effort to control the size, shape, and size distribution of Gd MOF nanoparticles, hydrotropes were incorporated into the reverse microemulsion synthesis used to produce these nanoparticles. A study of how hydrotropes influenced the mechanism of formation of reverse micelles offered a great deal of information with respect to the physical properties of the Gd MOF nanoparticles formed. Specifically, this study incorporated the hydrotropes, sodium salicylate (NaSal), 5-methyl salicylic acid, and salicylic acid into the reverse microemulsion. Results demonstrated that addition of each of the hydrotropes into the synthesis of Gd MOFs provided a simple route to control the nanoparticle size as a function of hydrotrope concentration. Specifically, Gd MOF nanoparticles synthesized with NaSal showed the best reduction in size distributions in both length and width with percent relative standard deviations being nearly 50% less than nanoparticles produced via the standard route from the literature. Finally, the effect of the size of the Gd MOF nanoparticles with respect to their MRI relaxation properties was evaluated. Initial results indicated a positive correlation between the surface areas of the Gd MOF nanoparticles with the longitudinal relaxivity in MRI. In particular, Gd MOF nanoparticles with an average size of 82 nm with the addition of NaSal, yielded a longitudinal relaxivity value of 83.9 mM⁻¹ [Gd³⁺] sec⁻¹, one of the highest reported values compared to other Gd-based nanoparticles in the literature to date.
[Show abstract][Hide abstract] ABSTRACT: A novel surface modification technique was employed to produce a polymer modified positive contrast agent nanoparticle through attachment of well-defined homopolymers synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A range of RAFT homopolymers including poly[N-(2-hydroxypropyl)methacrylamide], poly(N-isopropylacrylamide), polystyrene, poly(2-(dimethylamino)ethyl acrylate), poly(((poly)ethylene glycol) methyl ether acrylate), and poly(acrylic acid) were synthesized and subsequently used to modify the surface of gadolinium (Gd) metal-organic framework (MOF) nanoparticles. Employment of a trithiocarbonate RAFT agent allowed for reduction of the polymer end groups under basic conditions to thiolates, providing a means of homopolymer attachment through vacant orbitals on the Gd3+ ions at the surface of the Gd MOF nanoparticles. Magnetic resonance imaging (MRI) confirmed the relaxivity rates of these novel polymer modified structures were easily tuned by changes in the molecular weight and chemical structures of the polymers. When a hydrophilic polymer was used for modification of the Gd MOF nanoparticles, an increase in molecular weight of the polymer provided a respective increase in the longitudinal relaxivity. These relaxivity values were significantly higher than both the unmodified Gd MOF nanoparticles and the clinically employed contrast agents, Magnevist and Multihance, which confirmed the construct's ability to be utilized as a positive contrast nanoparticle agent in MRI. Further characterization confirmed that increased hydrophobicity of the polymer coating on the Gd MOF nanoparticles yielded minimal changes in the longitudinal relaxivity properties but large increases in the transverse relaxivity properties in the MRI.
[Show abstract][Hide abstract] ABSTRACT: Novel nanoscale theragnostic devices were successfully prepared through attachment of well defined, multifunctional polymer chains to gadolinium (Gd) metal-organic framework (MOF) nanoparticles. Copolymers of poly(N-isopropylacrylamide)-co-poly(N-acryloxysuccinimide)-co-poly(fluorescein O-methacrylate) were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. The succinimide functionality was utilized as a scaffold for attachment of both a therapeutic agent, such as methotrexate, and a targeting ligand, such as H-glycine-arginine-glycine-aspartate-serine-NH(2) peptide. Employment of a trithiocarbonate RAFT agent allowed for reduction of the polymer end groups to thiolates providing a means of copolymer attachment through vacant orbitals on the Gd(3+) ions at the surface of the Gd MOF nanoparticles. These versatile, nanoscale scaffolds were shown to be biocompatible and have cancer cell targeting, bimodal imaging, and disease treatment capabilities. This unique method provided a simple yet versatile route of producing polymer-nanoparticle theragnostic materials with an unprecedented degree of flexibility in the construct, potentially allowing for tunable loading capacities and spatial loading of targeting/treatment agents, while incorporating bimodal imaging capabilities through both magnetic resonance and fluorescence microscopy.
[Show abstract][Hide abstract] ABSTRACT: Poly(acrylic acid) (PAA) surface-modified gold nanorods, contained in deionized ultra filtered (DIUF) water, served as templates
for the formation of gold (Au), palladium (Pd), and platinum (Pt) nanoparticles upon reduction with NaBH4. This provided nanoparticles with respective diameters of 7.0±0.7, 4.1±0.4, and 5.1±0.5nm. Varying amounts of Pt metal
salt were used in EG, which acts as both a solvent and a reducing agent, ranging from 0.1, 0.2, and 1.0mg/mL, to provide
control over nanoparticle diameters of 2.0±0.5nm, to 4.0±0.5nm, and 6.2±1.9nm, respectively. Nanoparticle diameter
was also controlled in DIUF water by varying the amount of Pt metal salt from 0.1, 0.2, and 1.0mg/mL, producing Pt particle
diameters, respectively, increasing from 2.7±0.3nm to 4.1±0.5nm, and 6.0±0.6nm.
KeywordsSurface modification-Metallic nanoparticles-RAFT-Nanoparticle synthesis-Poly(acrylic acid)-Ethylene glycol
Journal of Nanoparticle Research 03/2009; 12(3):915-930. DOI:10.1007/s11051-009-9642-x · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The synthesis of diblock copolymer brushes, including poly(styrene) (PSty)-b-PSty, PSty-b-poly(acrylic acid), PSty-b-poly(N-isopropylacrylamide), and poly(methyl acrylate)-b-poly(N,N-(dimethylamino)ethyl acrylate), was achieved utilizing a combination of surface-mediated atom transfer radical polymerization (ATRP) and reversible addition−fragmentation chain transfer (RAFT) polymerization techniques. Conversion of bromine end groups of homopolymer brushes formed by ATRP via a modified atom transfer addition reaction to a RAFT agent and diblock extension via RAFT polymerization allowed the direct formation of well-defined stimuli-responsive diblock copolymer brushes. The addition of sacrificial initiator and/or chain transfer agent permitted formation of well-defined diblock copolymer brushes and free polymer chains in solution. The free polymer chains were isolated and used to estimate the molecular weights and polydispersity index of chains attached to the surface. Ellipsometry, contact angle measurements, grazing angle attenuated total reflectance−Fourier transform infrared spectroscopy, and wide-scan X-ray photoelectron spectroscopy (XPS) were used to characterize initiator deposition, homopolymer brush formation via ATRP, conversion to macro-RAFT agent, and diblock copolymer brush formation via RAFT polymerization. Selective solvent treatment demonstrated the stimuli-responsive nature of the diblock copolymer brushes via changes in the water contact angles and wide-scan XPS atomic percentages.
[Show abstract][Hide abstract] ABSTRACT: We present an account of our research into polyelectrolyte polymer brushes that are capable of acting as stimuli-responsive films. We first detail the synthesis of poly(acrylic acid) polymer brushes using ATRP in a "grafting from" strategy. Significantly, we employed a chemical-free deprotection step that should leave the anchoring ester groups intact. We have demonstrated how these polymer assemblies respond to stimuli such as pH and electrolyte concentration. We have used poly(acrylic acid) polymer brushes for the synthesis of metallic nanoparticles and review this work. We have used XPS, ATR-FTIR, and AFM spectroscopy to show the presence of silver and palladium nanoparticles within polymer brushes. Finally, we report the synthesis of AB diblock polyampholyte polymer brushes that represent an extension of polyelectrolyte polymer brushes.
[Show abstract][Hide abstract] ABSTRACT: The synthesis of a variety of well-defined diblock copolymer brushes, including poly(methyl methacrylate) (PMMA)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), PMMA-b-poly(styrene) (PSty), and PSty-b-poly(methyl acrylate), was achieved via surface immobilized reversible addition−fragmentation chain transfer (RAFT) polymerization. Initially, silicon surfaces were modified with RAFT chain transfer agents (CTAs) by utilizing a modified atom transfer addition reaction involving a silicon wafer modified with (11-(2-bromo-2-methyl)propionyloxy)undecyltrichlorosilane and dithiobenzoyl disulfide. Diblock copolymer brushes were then prepared via sequential surface initiated RAFT polymerization from the immobilized CTA. Various characterization techniques including ellipsometry, contact angle measurements, grazing angle attenuated total reflectance−Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy were used to characterize the immobilization of CTAs on the silicon wafer and the subsequent polymer formation. The addition of free CTA was required for the formation of well-defined diblock copolymer brushes, which subsequently resulted in the presence of free polymer chains in solution. The free polymer chains were isolated and used to estimate the molecular weights and polydispersity index of chains attached to the surface.
[Show abstract][Hide abstract] ABSTRACT: Herein we describe the surface modification of gold nanorods via the postpolymerization immobilization of polymers prepared by reversible addition−fragmentation chain transfer (RAFT). Gold nanorods have been synthesized via a three-step seed-mediated process and then subsequently modified with RAFT-preformed poly(2-(dimethylamino)ethyl methacrylate), poly(acrylic acid), and polystyrene homopolymers, with and without the use of reducing agents. Transmission electron microscopy has been used to visually monitor nanorod formations and UV−visible spectroscopy has been used to observe the absorption properties of nanorod formations. Both techniques monitored nanorods with and without surface modifications. This research provides a general and versatile technique for the surface modification of gold nanorods utilizing a wide range of polymers. Polymer modification of nanorods will potentially aid in nanorod self-assembly and ordering processes.
Chemistry of Materials 12/2006; 19(1). DOI:10.1021/cm0622912 · 8.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two distinct oligomeric species of similar mass and chemical functionality (M
w≈2,000g/mol), one a linear methyl methacrylate oligomer (radius of gyration R
g≈1.1nm) and the other a hybrid organic–inorganic polyhedral silsesquioxane nanocage (methacryl-POSS, r≈1.0nm), were subjected to thermal and rheological tests to compare the behaviors of these geometrically dissimilar molecules over the entire composition range. The glass transition temperatures of the blends varied monotonically between the glass transition temperatures of the pure oligomer (T
g=−47.3°C) and the pure POSS (T
g=−61.0°C). Blends containing high POSS contents (with volume fraction φ
POSS≥0.90) exhibited enhanced enthalpy relaxation in differential scanning calorimetry (DSC) measurements, and the degree of enthalpy relaxation was used to calculate the kinetic fragility indices m of the oligomeric MMA (m=59) and the POSS (m=74). The temperature dependences of the viscosities were fitted by the free-volume based Williams–Landel–Ferry (WLF) and Vogel–Fulcher–Tammann (VFT) framework and a dynamic scaling relation. The calculated values of the fragility from the WLF–VFT fits were similar for the POSS (m=82) and for the oligomer (m=76), and the dynamic scaling exponent was similar for the oligomeric MMA and the POSS. Within the range of known fragilities for glass-forming liquids, the temperature dependence of the viscosity was found to be similarly fragile for the two species. The difference in shape of the nanocages and oligomer chains is unimportant in controlling the glass-forming properties of the blends at low volume fractions (φ
POSS<0.20). However, at higher volume fractions, adjacent POSS cages begin to crowd each other, leading to an increase in the fractional free volume at the glass transition temperature and the observed enhanced enthalpy relaxation in DSC.
[Show abstract][Hide abstract] ABSTRACT: We report the preparation of a poly(acrylic acid) polymer brush from a flat silica substrate using a surface-initiated atom transfer radical polymerization of tert-butyl acrylate. Significantly, we use a chemical free deprotection strategy through pyrolysis of the tert-butyl esters to the corresponding carboxylic acids. This eliminates the possibility of loss of the polymer brush from the surface via acidolysis of the ester group in the surface bound initiator. We have verified the formation of the poly(acrylic acid) brush through ATR-FTIR, ellipsometry, water contact angle analysis, and XPS. We also demonstrate the stimuli-responsive nature of these brushes with respect to pH and added electrolyte concentration.
[Show abstract][Hide abstract] ABSTRACT: The surface rearrangement of polymer brushes composed of diblock copolymer chains with fluoropolymer blocks has been shown to be readily induced using thermal annealing. Changes in surface composition accomplished by the rearrangement were demonstrated by tensiometry and atomic force microscopy (AFM). Most of the research focused on brushes consisting of a hydrocarbon inner block [either poly(methyl acrylate) or polystyrene] and a fluoropolymer outer block [poly(pentafluorostyrene), poly(heptadecafluorodecyl acrylate), poly(pentafluoropropyl acrylate), or poly(trifluoroethyl acrylate)]. The diblock copolymer brushes were first treated with a block selective solvent for the hydrocarbon block. Rearrangement was complete for all brushes except those in which poly(heptadecafluorodecyl acrylate) was the outer block. Subsequentially, the surfaces were then thermally treated to allow the fluoropolymer to migrate to the surface. The optimal temperature and exposure time for thermal treatment were found to vary with the glass transition temperatures (Tg). The poly(methyl acrylate)-b-poly(pentafluoropropyl acrylate) brush exhibited the most complete surface rearrangement upon solvent treatment and the fastest rearrangement upon thermal treatment. The thermal rearrangement of a poly(2-hydroxyethyl methacrylate)-b-poly(methyl acrylate) brush that was reacted with heptafluorobutyryl chloride via an acylation reaction was also studied. Fluoropolymer-rich surfaces created by thermal rearrangement were rougher than those created by solvent rearrangement.