Controlling Mechanical Properties of Medical-Grade Scaffolds through Electrospinning Parameter Selection.

Electrospinning (ES) is a versatile process mode for creating fibrous materials with various structures that have broad applications ranging from regenerative medicine to tissue engineering and surgical mesh implants. The recent commercialization of this technology for implant use has driven the use of resorbable electrospun products. Resorbable electrospun meshes offer great promise as temporary implants that can utilize the layer upon layer method of additive manufacturing to incorporate porosity as a function of process parameters into a scaffold structure. The interconnected porosity and feature size known to ES have previously been observed to hold great potential for simulating the natural cellular environment of soft tissue. This microstructure, proper degradation kinetics, and mechanical properties combine to provide the design basis for artificial tissue structures that could aid in not only wound healing but also true tissue engineering and regenerative medicine. While current advancement in the field is understood to be limited by material properties, the importance of optimizing mechanical properties with currently available materials should not be overlooked. This work investigated the process parameter effects and interactions that control the structure-property relationship for a range of medical-grade aliphatic polyester materials with a range of intrinsic properties. An ε-caprolactone homopolymer (PCL), l-lactide homopolymer (PLLA), and Lactoflex, a copolymer with intermediate properties relative to the homopolymers, were characterized before, during, and after the additive manufacturing process. The interacting effects of process parameters, distance to collector, and dispensing rate were shown to produce variable-density, nonwoven scaffold structures. The resorbable mesh scaffolds of PLLA, PCL, and Lactoflex demonstrated a broad range of mechanical properties (approximately 1-10 MPa ultimate tensile strength and 5-390 MPa tensile modulus). Postprocessing of scaffolds demonstrated removal of solvents and preservation of micrometer-sized features. Resorbable polymers and electrospinning can produce scaffold materials with excellent features and offer tremendous potential in the field of implantable resorbable devices.

Polypyrrole Coating via Lemieux-von Rudloff Oxidation on Magnetite Nanoparticles for Highly Efficient Removal of Chromium(VI) from Wastewater.

An alternative way for the coating of polypyrrole (PPy) polymer on hydrophobic magnetite (Fe3O4) nanoparticles is reported here to capture toxic chromium ions, Cr (VI), present in water. Iron oxide magnetic nanoparticles (Fe3O4) were synthesized by the conventional coprecipitation technique using FeCl3·6H2O and FeSO4·7H2O iron precursors and subsequently modified with oleic acid (OA). Then OA-Fe3O4 hydrophobic nanoparticles were oxidized using the Lemieux-von Rudloff reaction to transfer OA into hydrophilic azelaic acid (AA) (HOOC(CH2)7COOH-modified magnetic nanoparticles (AA-Fe3O4). Finally, a PPy polymer coating was formed by a seeded polymerization of pyrrole, using AA-Fe3O4 as seeds. The average size of PPy/Fe3O4 nanocomposites is 12.33 nm and is almost spherical in shape. The surface composition is confirmed by FTIR and thermogravimetry analyses. An X-ray diffraction study confirmed the formation of highly crystalline Fe3O4 nanoparticles, and the crystallinity was retained after the surface modification. The adsorption study suggested that the Cr(VI) ion adsorption is highly pH-dependent and the maximum amount of adsorption is obtained at pH 2.0. The adsorption results revealed that the Langmuir model provided the best fit for the isotherm, with a maximum adsorption capacity reaching approximately 173.22 mg g-1 at 323 K. Spontaneous and endothermic adsorption processes were confirmed by evaluating the thermodynamic parameters obtained in this investigation. The kinetics study showed that the interaction between Cr(VI) ions and magnetic nanocomposites was directed by a pseudo-second-order rate process indicating chemisorption. The prepared PPy/Fe3O4 nanocomposites would be promising adsorbents to purify water by eliminating Cr(VI) metal ions from wastewater.

Facile Fabrication and Characterization of Amine-Functional Silica Coated Magnetic Iron Oxide Nanoparticles for Aqueous Carbon Dioxide Adsorption.

Surface active amine-functionalized silica coated magnetic iron oxide nanoparticles were prepared by a simple two-step process for adsorbing CO2 gas from aqueous medium. First, oleic acid (OA) coated iron oxide magnetic particles (denoted as Fe3O4-OA) were prepared by a simple coprecipitation method. Then, the surface of the Fe3O4-OA particles was coated with silica by using tetraethyl orthosilicate. Finally, aminated Fe3O4/SiO2-NH2 nanoparticles were concomitantly formed by the reactions of 3-aminopropyl triethoxysilane with silica-coated particles. The formation of materials was confirmed by Fourier transform infrared spectral analysis. Transmission electron microscopic analysis revealed both spherical and needle-shaped morphologies of magnetic Fe3O4/SiO2-NH2 particles with an average size of 15 and 68.6 nm, respectively. The saturation magnetization of Fe3O4/SiO2-NH2 nanoparticles was found to be 33.6 emu g-1, measured by a vibrating sample magnetometer at ambient conditions. The crystallinity and average crystallite size (7.0 nm) of the Fe3O4/SiO2-NH2 particles were revealed from X-ray diffraction data analyses. Thermogravimetric analysis exhibited good thermal stability of the nanoadsorbent up to an elevated temperature. Zeta potential measurements revealed pH-sensitive surface activity of Fe3O4/SiO2-NH2 nanoparticles in aqueous medium. The produced magnetic Fe3O4/SiO2-NH2 nanoparticles also exhibited efficient proton capturing activity (92%). The particles were used for magnetically recyclable adsorption of aqueous CO2 at different pH values and temperatures. Fe3O4/SiO2-NH2 nanoparticles demonstrated the highest aqueous CO2 adsorption efficiency (90%) at 40 °C, which is clearly two times higher than that of nonfunctionalized Fe3O4-OA particles.

Construction of a corresponding empirical model to bridge thermal properties and synthesis of thermoresponsive poloxamines.

The thermoresponsive properties of poloxamine (tetra-branch PEO-PPO block copolymer) hydrogels are related to several variables. Of particular interest to this study were the molecular weight of the polymer, the molar ratio between PEO and PPO blocks, and the concentration of the aqueous solution. Accurately controlling the thermoresponsive behaviors of the polymer is critical to the application of such materials; therefore, the structure-property relationship of tetra-branch PEO-PPO block copolymer was studied by synthesis via anionic ring-opening polymerization (AROP). The structure-property relationships were studied by measuring the thermoresponsive behavior via differential scanning calorimetry (DSC) and developing an empirical model which statistically fit the collected data. This empirical model was then used for designing poloxamines that have critical micellization temperatures (CMT) between room temperature and physiological temperature. The model was validated with three polymers that targeted a CMT of 308 K (35°C). The empirical model showed great success in guiding the synthesis of poloxamines showing a temperature difference of less than 3 K between the predicted and the observed CMTs. This study showed a great potential of using an empirical model to set synthesis parameters to control the properties of the polymer products.

Recent advances in zinc ferrite (ZnFe2O4) based nanostructures for magnetic hyperthermia applications.

Spinel ferrite-based magnetic nanomaterials have been investigated for numerous biomedical applications, including targeted drug delivery, magnetic hyperthermia therapy (MHT), magnetic resonance imaging (MRI), and biosensors, among others. Recent studies have found that zinc ferrite-based nanomaterials are favorable candidates for cancer theranostics, particularly for magnetic hyperthermia applications. Zinc ferrite exhibits excellent biocompatibility, minimal toxicity, and more importantly, exciting magnetic properties. In addition, these materials demonstrate a Curie temperature much lower than other transition metal ferrites. By regulating synthesis protocols and/or introducing suitable dopants, the Curie temperature of zinc ferrite-based nanosystems can be tailored to the MHT therapeutic window, i.e., 43-46 °C, a range which is highly beneficial for clinical hyperthermia applications. Furthermore, zinc ferrite-based nanostructures have been extensively used in successful pre-clinical trials on mice models focusing on the synergistic killing of cancer cells involving magnetic hyperthermia and chemotherapy. This review provides a systematic and comprehensive understanding of the recent developments of zinc ferrite-based nanomaterials, including doped particles, shape-modified structures, and composites for magnetic hyperthermia applications. In addition, future research prospects involving pure ZnFe2O4 and its derivative nanostructures have also been proposed.

A Novel Bio-Adhesive Mesh System for Medical Implant Applications: In Vivo Assessment in a Rabbit Model.

Injectable surgical sealants and adhesives, such as biologically derived fibrin gels and synthetic hydrogels, are widely used in medical products. While such products adequately adhere to blood proteins and tissue amines, they have poor adhesion with polymer biomaterials used in medical implants. To address these shortcomings, we developed a novel bio-adhesive mesh system utilizing the combined application of two patented technologies: a bifunctional poloxamine hydrogel adhesive and a surface modification technique that provides a poly-glycidyl methacrylate (PGMA) layer grafted with human serum albumin (HSA) to form a highly adhesive protein surface on polymer biomaterials. Our initial in vitro tests confirmed significantly improved adhesive strength for PGMA/HSA grafted polypropylene mesh fixed with the hydrogel adhesive compared to unmodified mesh. Toward the development of our bio-adhesive mesh system for abdominal hernia repair, we evaluated its surgical utility and in vivo performance in a rabbit model with retromuscular repair mimicking the totally extra-peritoneal surgical technique used in humans. We assessed mesh slippage/contraction using gross assessment and imaging, mesh fixation using tensile mechanical testing, and biocompatibility using histology. Compared to polypropylene mesh fixed with fibrin sealant, our bio-adhesive mesh system exhibited superior fixation without the gross bunching or distortion that was observed in the majority (80%) of the fibrin-fixed polypropylene mesh. This was evidenced by tissue integration within the bio-adhesive mesh pores after 42 days of implantation and adhesive strength sufficient to withstand the physiological forces expected in hernia repair applications. These results support the combined use of PGMA/HSA grafted polypropylene and bifunctional poloxamine hydrogel adhesive for medical implant applications.

Effect of manganese substitution of ferrite nanoparticles on particle grain structure.

To investigate the influence of manganese substitution on the saturation magnetization of manganese ferrite nanoparticles, samples with various compositions (Mn x Fe3-x O4, x = 0, 0.25, 0.5, 0.75, and 1) were synthesized and characterized. The saturation magnetization of such materials was both calculated using density functional theory and measured via vibrating sample magnetometry. A discrepancy was found; the computational data demonstrated a positive correlation between manganese content and saturation magnetization, while the experimental data exhibited an inverse correlation. X-ray diffraction (XRD) and magnetometry results indicated that the crystallite diameter and the magnetic diameter decrease when adding more manganese, which could explain the loss of magnetization of the particles. For 20 nm nanoparticles, with increasing manganese substitution level, the crystallite size decreases from 10.9 nm to 6.3 nm and the magnetic diameter decreases from 15.1 nm to 3.5 nm. Further high resolution transmission electron microscopy (HRTEM) analysis confirmed the manganese substitution induced defects in the crystal lattice, which encourages us to find ways of eliminating crystalline defects to make more reliable ferrite nanoparticles.

Best Practices for Characterization of Magnetic Nanoparticles for Biomedical Applications.

The use of magnetic nanoparticles in biomedical applications provides are a wealth of opportunities. Nonetheless, to truly understand the interactions of these materials in biological media, detailed characterization is necessary with these complex systems. This Feature highlights some "best practices" in the analytical techniques and challenges in the measurement of the properties of these materials.

The effect of post-synthesis aging on the ligand exchange activity of iron oxide nanoparticles.

HYPOTHESIS: Ligand exchange is a widely-used method of controlling the surface chemistry of nanomaterials. Exchange is dependent on many factors including the age of the core particle being modified. Aging of the particles can impact surface structure and composition, which in turn can affect ligand binding. EXPERIMENTS: To quantify the effects of aging on ligand exchange, we employed a technique to track the exchange of radiolabeled 14C-oleic acid with unlabeled, oleic acid bound to iron oxide nanoparticles. Liquid scintillation counting (LSC) was used to determine the amount of 14C-oleic acid adsorbing to the particles throughout the duration of the exchange for particles aged for 2days, 7days, and 30days. FINDINGS: Results revealed an increase in the total amount of ligands exchanged with aging up to 30days. Kinetic analysis of these results revealed a significant decrease in the overall rate of ligand exchange between 2 and 30days. The change in extent of adsorption with age could suggest increased availability of free binding sites. A follow-up study comparing exchange with oxidized and unoxidized particles suggested this increase in ligand adsorption may be due to changes in the Fe2+/Fe3+ ratio on the surface as the particles aged.

pH Triggered Recovery and Reuse of Thiolated Poly(acrylic acid) Functionalized Gold Nanoparticles with Applications in Colloidal Catalysis.

Thiolated poly(acrylic acid) (PAA-SH) functionalized gold nanoparticles were explored as a colloidal catalyst with potential application as a recoverable catalyst where the PAA provides pH-responsive dispersibility and phase transfer capability between aqueous and organic media. This system demonstrates complete nanoparticle recovery and redispersion over multiple reaction cycles without changes in nanoparticle morphology or reduction in conversion. The catalytic activity (rate constant) was reduced in subsequent reactions when recovery by aggregation was employed, despite unobservable changes in morphology or dispersibility. When colloidal catalyst recovery employed a pH induced phase transfer between two immiscible solvents, the catalytic activity of the recovered nanoparticles was unchanged over four cycles, maintaining the original rate constant and 100% conversion. The ability to recover and reuse colloidal catalysts by aggregation/redispersion and phase transfer methods that occur at low and high pH, respectively, could be used for different gold nanoparticle catalyzed reactions that occur at different pH conditions.

Bright X-ray and up-conversion nanophosphors annealed using encapsulated sintering agents for bioimaging applications.

Nanophosphors are promising contrast agents for deep tissue optical imaging applications because they can be excited by X-ray and near infrared light that penetrates deeply through tissue and generates almost no autofluorescence background in the tissue. For these bioimaging applications, the nanophosophors should ideally be small, monodispersed and brightly luminescent. However, most methods used to improve luminescence yield by annealing the particles to reduce crystal and surface defects (e.g. using flux or sintering agents) also cause particle fusion or require multiple component core-shell structures. Here, we report a novel method to prepare bright, uniformly sized X-ray nanophosphors (Gd2O2S:Eu or Tb) and upconversion nanophosphors (Y2O2S: Yb/Er, or Yb/Tm) with large crystal domain size without causing aggregation. A core-shell nanoparticle is formed, with NaF only in the core. We observe that increasing the NaF sintering agent concentration up to 7.6 mol% increases both crystal domain size and luminescence intensity (up to 40% of commercial microphosphors) without affecting the physical particticle diameter. Above 7.6 mol%, particle fusion is observed. The annealing is insensitive to the cation (Na+ or K+) but varies strongly with anion, with F->Cl->CO32->Br->I-. The luminescence depends strongly on crystal domain size. The data agree reasonably well with a simple domain surface quenching model, although the size-dependence suggests additional quenching mechanisms within small domains. The prepared bright nanophosphors were subsequently functionalized with PEG-folic acid to target MCF-7 breast cancer cells which overexpress folic acid receptors. Both X-ray and upconversion nanophosphors provided low background and bright luminescence which was imaged through 1 cm chicken breast tissue at a low dose of nanophosphors 200 µL (0.1 mg/mL). We anticipate these highly monodispersed and bright X-ray and upconversion nanophosphors will have significant potential for tumor targeted imaging.

Quantitative Measurement of Ligand Exchange with Small-Molecule Ligands on Iron Oxide Nanoparticles via Radioanalytical Techniques.

Ligand exchange on the surface of hydrophobic iron oxide nanoparticles is a common method for controlling surface chemistry for a desired application. Furthermore, ligand exchange with small-molecule ligands may be necessary to obtain particles with a specific size or functionality. Understanding to what extent ligand exchange occurs and what factors affect it is important for the optimization of this critical procedure. However, quantifying the amount of exchange may be difficult because of the limitations of commonly used characterization techniques. Therefore, we utilized a radiotracer technique to track the exchange of a radiolabeled 14C-oleic acid ligand with hydrophilic small-molecule ligands on the surface of iron oxide nanoparticles. Iron oxide nanoparticles functionalized with 14C-oleic acid were modified with small-molecule ligands with terminal functional groups including catechols, phosphonates, sulfonates, thiols, carboxylic acids, and silanes. These moieties were selected because they represent the most commonly used ligands for this procedure. The effectiveness of these molecules was compared using both procedures widely found in the literature and using a standardized procedure. After ligand exchange, the nanoparticles were analyzed using liquid scintillation counting (LSC) and inductively coupled plasma-mass spectrometry. The labeled and unlabeled particles were further characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) to determine the particle size, hydrodynamic diameter, and zeta potential. The unlabeled particles were characterized via attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and vibrating sample magnetometry (VSM) to confirm the presence of the small molecules on the particles and verify the magnetic properties, respectively. Radioanalytical determination of 14C-oleic acid was used to calculate the total amount of oleic acid remaining on the surface of the particles after ligand exchange. The results revealed that the ligand-exchange reactions performed using widely cited procedures did not go to completion. Residual oleic acid remained on the particles after these reactions and the reactions using a standardized protocol. A comparison of the ligand-exchange procedures indicated that the binding moiety, multidenticity, reaction time, temperature, and presence of a catalyst impacted the extent of exchange. Quantification of the oleic acid remaining after ligand exchange revealed a binding hierarchy in which catechol-derived anchor groups displace the most oleic acid on the surface of the nanoparticles and the thiol group displaces the least amount of oleic acid. Thorough characterization of ligand exchange is required to develop nanoparticles suitable for their intended application.

Superfine powdered activated carbon (S-PAC) coatings on microfiltration membranes: Effects of milling time on contaminant removal and flux.

In microfiltration processes for drinking water treatment, one method of removing trace contaminants is to add powdered activated carbon (PAC). Recently, a version of PAC called superfine PAC (S-PAC) has been under development. S-PAC has a smaller particle size and thus faster adsorption kinetics than conventionally sized PAC. Membrane coating performance of various S-PAC samples was evaluated by measuring adsorption of atrazine, a model micropollutant. S-PACs were created in-house from PACs of three different materials: coal, wood, and coconut shell. Milling time was varied to produce S-PACs pulverized with different amounts of energy. These had different particles sizes, but other properties (e.g. oxygen content), also differed. In pure water the coal based S-PACs showed superior atrazine adsorption; all milled carbons had over 90% removal while the PAC had only 45% removal. With addition of calcium and/or NOM, removal rates decreased, but milled carbons still removed more atrazine than PAC. Oxygen content and specific external surface area (both of which increased with longer milling times) were the most significant predictors of atrazine removal. S-PAC coatings resulted in loss of filtration flux compared to an uncoated membrane and smaller particles caused more flux decline than larger particles; however, the data suggest that NOM fouling is still more of a concern than S-PAC fouling. The addition of calcium improved the flux, especially for the longer-milled carbons. Overall the data show that when milling S-PAC with different levels of energy there is a tradeoff: smaller particles adsorb contaminants better, but cause greater flux decline. Fortunately, an acceptable balance may be possible; for example, in these experiments the coal-based S-PAC after 30 min of milling achieved a fairly high atrazine removal (overall 80%) with a fairly low flux reduction (under 30%) even in the presence of NOM. This suggests that relatively short duration (low energy) milling is viable for creating useful S-PAC materials applied in tandem with microfiltration.

Effect of bead milling on chemical and physical characteristics of activated carbons pulverized to superfine sizes.

Superfine powdered activated carbon (S-PAC) is an adsorbent material with particle size between roughly 0.1-1 µm. This is about an order of magnitude smaller than conventional powdered activated carbon (PAC), typically 10-50 µm. S-PAC has been shown to outperform PAC for adsorption of various drinking water contaminants. However, variation in S-PAC production methods and limited material characterization in prior studies lead to questions of how S-PAC characteristics deviate from that of its parent PAC. In this study, a wet mill filled with 0.3-0.5 mm yttrium-stabilized zirconium oxide grinding beads was used to produce S-PAC from seven commercially available activated carbons of various source materials, including two coal types, coconut shell, and wood. Particle sizes were varied by changing the milling time, keeping mill power, batch volume, and recirculation rate constant. As expected, mean particle size decreased with longer milling. A lignite coal-based carbon had the smallest mean particle diameter at 169 nm, while the wood-based carbon had the largest at 440 nm. The wood and coconut-shell based carbons had the highest resistance to milling. Specific surface area and pore volume distributions were generally unchanged with increased milling time. Changes in the point of zero charge (pH(PZC)) and oxygen content of the milled carbons were found to correlate with an increasing specific external surface area. However, the isoelectric point (pH(IEP)), which measures only external surfaces, was unchanged with milling and also much lower in value than pH(PZC). It is likely that the outer surface is easily oxidized while internal surfaces remain largely unchanged, which results in a lower average pH as measured by pH(PZC).

Synthesis and application of glycoconjugate-functionalized magnetic nanoparticles as potent anti-adhesion agents for reducing enterotoxigenic Escherichia coli infections.

Polyethylene oxide stabilized magnetic nanoparticles (PEO-MNPs) bio-functionalized with glycoconjugate (Neu5Ac(α2-3)Gal(ß1-4)Glcß-sp) (GM3-MNPs) are synthesized using click chemistry. Interaction of GM3-MNPs with Enterotoxigenic Escherichia coli (ETEC) strain K99 (EC K99) is investigated using different microscopic techniques. Our results suggest that GM3-MNPs can effectively act as non-antibiotic anti-adhesion agents for treating ETEC infections.

Quantitative measurement of ligand exchange on iron oxides via radiolabeled oleic acid.

Ligand exchange of hydrophilic molecules on the surface of hydrophobic iron oxide nanoparticles produced via thermal decomposition of chelated iron precursors is a common method for producing aqueous suspensions of particles for biomedical applications. Despite the wide use, relatively little is understood about the efficiency of ligand exchange on the surface of iron oxide nanoparticles and how much of the hydrophobic ligand is removed. To address this issue, we utilized a radiotracer technique to track the exchange of a radiolabeled (14)C-oleic acid ligand with hydrophilic ligands on the surface of magnetite nanoparticles. Iron oxide nanoparticles functionalized with (14)C-oleic acid were modified with poly(ethylene glycol) with terminal functional groups including, L-3,4-dihydroxyphenylalanine, a nitrated L-3,4-dihydroxyphenylalanine, carboxylic acid, a phosphonate, and an amine. Following ligand exchange, the nanoparticles and byproducts were analyzed using liquid scintillation counting and inductively coupled plasma mass spectroscopy. The labeled and unlabeled particles were further characterized by transmission electron microscopy and dynamic light scattering to determine particle size, hydrodynamic diameter, and zeta potential. The unlabeled particles were characterized via thermogravimetric analysis and vibrating sample magnetometry. Radioanalytical determination of the (14)C from (14)C-oleic acid was used to calculate the amount of oleic acid remaining on the surface of the particles after purification and ligand exchange. There was a significant loss of oleic acid on the surface of the particles after ligand exchange with amounts varying for the different functional binding groups on the poly(ethylene glycol). Nonetheless, all samples demonstrated some residual oleic acid associated with the particles. Quantification of the oleic acid remaining after ligand exchange reveals a binding hierarchy in which catechol derived anchor groups displace oleic acid on the surface of the nanoparticles better than the phosphonate, followed by the amine and carboxylic acid groups. Furthermore, the results show that these ligand exchange reactions do not necessarily occur to completion as is often assumed, thus leaving a residual amount of oleic acid on the surface of the particles. A thorough analysis of ligand exchange is required to develop nanoparticles that are suitable for their desired application.

Multifunctional yolk-in-shell nanoparticles for pH-triggered drug release and imaging.

Multifunctional nanoparticles are synthesized for both pH-triggered drug release and imaging with radioluminescence, upconversion luminescent, and magnetic resonance imaging (MRI). The particles have a yolk-in-shell morphology, with a radioluminescent core, an upconverting shell, and a hollow region between the core and shell for loading drugs. They are synthesized by controlled encapsulation of a radioluminescent nanophosphor yolk in a silica shell, partial etching of the yolk in acid, and encapsulation of the silica with an upconverting luminescent shell. Metroxantrone, a chemotherapy drug, was loaded into the hollow space between X-ray phosphor yolk and up-conversion phosphor shell through pores in the shell. To encapsulate the drug and control the release rate, the nanoparticles are coated with pH-responsive biocompatible polyelectrolyte layers of charged hyaluronic acid sodium salt and chitosan. The nanophosphors display bright luminescence under X-ray, blue light (480 nm), and near infrared light (980 nm). They also served as T1 and T2 MRI contrast agents with relaxivities of 3.5 mM(-1) s(-1) (r1 ) and 64 mM(-1) s(-1) (r2 ). These multifunctional nanocapsules have applications in controlled drug delivery and multimodal imaging.

Iron-Loaded Magnetic Nanocapsules for pH-Triggered Drug Release and MRI Imaging.

Magnetic nanocapsules were synthesized for controlled drug release, magnetically assisted delivery, and MRI imaging. These magnetic nanocapsules, consisting of a stable iron nanocore and a mesoporous silica shell, were synthesized by controlled encapsulation of ellipsoidal hematite in silica, partial etching of the hematite core in acid, and reduction of the core by hydrogen. The iron core provided a high saturation magnetization and was stable against oxidation for at least 6 months in air and 1 month in aqueous solution. The hollow space between the iron core and mesoporous silica shell was used to load anticancer drug and a T1-weighted MRI contrast agent (Gd-DTPA). These multifunctional monodispersed magnetic "nanoeyes" were coated by multiple polyelectrolyte layers of biocompatible poly-l-lysine and sodium alginate to control the drug release as a function of pH. We studied pH-controlled release, magnetic hysteresis curves, and T1/T2 MRI contrast of the magnetic nanoeyes. They also served as MRI contrast agents with relaxivities of 8.6 mM-1 s-1 (r1) and 285 mM-1 s-1 (r2).

The formation of linear aggregates in magnetic hyperthermia: implications on specific absorption rate and magnetic anisotropy.

The design and application of magnetic nanoparticles for use as magnetic hyperthermia agents has garnered increasing interest over the past several years. When designing these systems, the fundamentals of particle design play a key role in the observed specific absorption rate (SAR). This includes the particle's core size, polymer brush length, and colloidal arrangement. While the role of particle core size on the observed SAR has been significantly reported, the role of the polymer brush length has not attracted as much attention. It has recently been reported that for some suspensions linear aggregates form in the presence of an applied external magnetic field, i.e. chains of magnetic particles. The formation of these chains may have the potential for a dramatic impact on the biomedical application of these materials, specifically the efficiency of the particles to transfer magnetic energy to the surrounding cells. In this study we demonstrate the dependence of SAR on magnetite nanoparticle core size and brush length as well as observe the formation of magnetically induced colloidal arrangements. Colloidally stable magnetic nanoparticles were demonstrated to form linear aggregates in an alternating magnetic field. The length and distribution of the aggregates were dependent upon the stabilizing polymer molecular weight. As the molecular weight of the stabilizing layer increased, the magnetic interparticle interactions decreased therefore limiting chain formation. In addition, theoretical calculations demonstrated that interparticle spacing has a significant impact on the magnetic behavior of these materials. This work has several implications for the design of nanoparticle and magnetic hyperthermia systems, while improving understanding of how colloidal arrangement affects SAR.

Synthesis of brightly PEGylated luminescent magnetic upconversion nanophosphors for deep tissue and dual MRI imaging.

A method is developed to fabricate monodispersed biocompatible Yb/Er or Yb/Tm doped ß-NaGdF4 upconversion phosphors using polyelectrolytes to prevent irreversible particle aggregation during conversion of the precursor, Gd2 O(CO3 )2.H2 O:Yb/Er or Yb/Tm, to ß-NaGdF4 :Yb/Er or Yb/Tm. The polyelectrolyte on the outer surface of nanophosphors also provided an amine tag for PEGylation. This method is also employed to fabricate PEGylated magnetic upconversion phosphors with Fe3 O4 as the core and ß-NaGdF4 as a shell. These magnetic upconversion nanophosphors have relatively high saturation magnetization (7.0 emu g(-1) ) and magnetic susceptibility (1.7 × 10(-2) emu g(-1) Oe(-1) ), providing them with large magnetophoretic mobilities. The magnetic properties for separation and controlled release in flow, their optical properties for cell labeling, deep tissue imaging, and their T1 - and T2 -weighted magnetic resonance imaging (MRI) relaxivities are studied. The magnetic upconversion phosphors display both strong magnetophoresis, dual MRI imaging (r1 = 2.9 mM(-1) s(-1) , r2 = 204 mM(-1) s(-1) ), and bright luminescence under 1 cm chicken breast tissue.