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- Fornara, Andrea, 1980-, et al.
(author)
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Polymeric/inorganic multifunctional nanoparticles for simultaneous drug delivery and visualization
- 2010
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In: Materials Research Society Symposium Proceedings. - 0272-9172 .- 1946-4274. ; 1257
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Journal article (peer-reviewed)abstract
- Nanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.
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| 2. |
- Li, Shanghua, et al.
(author)
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Synthesis and magnetic properties of bulk transparent PMMA/Fe-oxide nanocomposites
- 2009
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In: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 20:18
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Journal article (peer-reviewed)abstract
- PMMA/Fe-oxide nanocomposites are fabricated by a chemical method. Monodispersed Fe-oxide nanoparticles are well dispersed in the PMMA matrix by in situ polymerization, resulting in a bulk transparent polymeric nanocomposite. The magnetic behavior of the PMMA/Fe-oxide nanocomposites is investigated. The transparent PMMA/Fe-oxide nanocomposite has potentially interesting magneto-optic applications without compromising the advantages of a lightweight, noncorrosive polymeric material with very high transparency even for bulk samples.
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| 3. |
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| 4. |
- Fornara, Andrea, 1980-
(author)
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Magnetic nanostructured materials for advanced bio-applications
- 2008
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Licentiate thesis (other academic/artistic)abstract
- In the recent years, nanostructured magnetic materials and their use in biomedical and biotechnological applications have received a lot of attention. In this thesis, we developed tailored magnetic nanoparticles for advanced bio-applications, such as direct detection of antibodies in biological samples and stimuli responsive drug delivery system. For sensitive and selective detection of biomolecules, thermally blocked iron oxide nanoparticles with specific magnetic properties are synthesized by thermal hydrolysis to achieve a narrow size distribution just above the superparamagnetic limit. The prepared nanoparticles were characterized and functionalized with biomolecules for use in a successful biosensor system. We have demonstrated the applicability of this type of nanoparticles for the detection of Brucella antibodies as model compound in serum samples and very low detection limits were achieved (0.05 mg/mL). The second part is concerning an in-depth investigation of the evolution of the thermally blocked magnetic nanoparticles. In this study, the formation of the nanoparticles at different stages during the synthesis was investigated by high resolution electron microscopy and correlated to their magnetic properties. At early stage of the high temperature synthesis, small nuclei of 3.5 nm are formed and the particles size increases successively until they reach a size of 17-20 nm. The small particles first exhibit superparamagnetic behavior at the early stage of synthesis and then transform to thermally blocked behavior as their size increases and passes the superparamagnetic limit. The last section of the Thesis is related to the development of novel drug delivery system based on magnetically controlled release rate. The system consists of hydrogel of Pluronic FP127 incorporating superparamagnetic iron oxide nanoparticles to form a ferrogel. The sol to gel formation of the hydrogel could be tailored to be solid at body temperature and thus have the ability to be injected inside living biological tissues. In order to evaluate the drug loading and release, the hydrophobic drug indomethacin was selected as a model compound. The drug could be loaded in the ferrogel owning to the oil in water micellar structure. We have studied the release rate from the ferrogel in the absence and presence of magnetic field. We have demonstrated that the drug release rate can be significantly enhanced by use of external magnetic field decreasing the half time of the release to more than 50% (from 3200 to 1500 min) upon the application of the external magnetic field. This makes the developed ferrogel a very promising drug delivery system that does not require surgical implant procedure for medical treatment and gives the possibility of enhancing the rate of release by external magnetic field.
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| 5. |
- Fornara, Andrea, 1980-
(author)
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Multifunctional nanomaterials for diagnostic and therapeutic applications
- 2010
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Doctoral thesis (other academic/artistic)abstract
- In the past few years, the use of nanostructured materials in medical applications hasdramatically increased, both in the research phase and for clinical purposes, due to thepeculiar properties and the ability of such materials to interact at a similar scale withbiological entities. In this thesis, we developed tailored magnetic multifunctionalnanoparticles for diagnostic and therapeutic applications, such as detection ofbiomolecules, simultaneous enhanced magnetic resonance imaging (MRI), fluorescentvisualization and controlled drug release.For sensitive and selective detection of specific biomolecules, thermally blocked ironoxide nanoparticles with tailored magnetic properties were developed. The formation ofsuch nanoparticles has been studied both in terms of size and magnetic behavior in liquidsuspension or in polymer matrixes. These particles with narrow size distribution (averagediameter of 19 nm) were surface functionalized by antigen molecules and were used forthe detection of Brucella antibodies in biological samples. The binding of biomoleculesresults in an increase in the particle’s hydrodynamic diameter, affecting the relaxationbehavior that was monitored by magnetic measurements. This sensing system is a fastand sensitive biosensor with very low detection limits (0.05 μg/mL).Superparamagnetic iron oxide nanoparticles (SPION) have been synthesized withaverage diameter of 10-12 nm, narrow size distribution, high crystallinity and superiormagnetic properties as liquid suspensions or embedded in a bulk transparent magneticnanocomposite. These nanoparticles were synthesized in organic solvents and, after phasetransfer with Pluronic F127 amphiphilic copolymer, show excellent relaxivity properties(high r2/r1 ratio) and great contrast enhancement in T2 weighted MRI, confirmed by invivostudies of rat inner ear.SPION have been used as a component for different multifunctional nanostructures. Thefirst system based on poly (L,L lactide)-methoxy polyethylene glycol (PLLA-mPEG)copolymer has been prepared by an emulsion/evaporation process that lead to polymericnanoparticles containing several imaging agents, such as SPION, quantum dots (QDs)and gold nanorods as well as indomethacin (IMC) as therapeutic payload. With a similarprocedure, but using poly (lactide-co-glycolide) (PLGA-PEG-NH2) copolymer, a secondtype of multifunctional nanoparticles has been obtained. Their size can be tailored from70 to 150 nm varying synthesis parameters, such as the surfactant concentration or waterto oil ratio. Both these polymer-based multifunctional nanoparticles can be visualized byfluorescence microscopy (QDs photoemission) and MRI (SPION magnetization) and theycan be used for photothermal therapy (gold nanorods) and drug delivery. The last systemconsists of SPION nanoparticles coated with PLLA directly on the surface by an in-situpolymerization process. A hydrophobic drug was loaded before the phase transfer withPluronic F127 and these nanoparticles show simultaneous MRI T2 contrast enhancementas well as high drug loading and sustained delivery.Controlling the drug release rate is also a critical parameter for tailored therapeutictreatments, and for this reason we developed a novel drug delivery system based on theintegration of SPION and Pluronic F127 gels. IMC was loaded in the ferrogel (with atailored gelation temperature) and its release rate was triggered by applying an externalmagnetic field owing to the SPION magnetic properties.
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| 8. |
- Thaler, Marlene, et al.
(author)
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Visualization and Analysis of Superparamagnetic Iron Oxide Nanoparticles in the Inner Ear by Light Microscopy and Energy Filtered TEM
- 2011
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In: Nanomedicine: Nanotechnology, Biology, and Medicine. - : Elsevier BV. - 1549-9634. ; 7:3, s. 360-369
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Journal article (peer-reviewed)abstract
- Nanoparticles as potential carriers for local drug transfer are an alternative to systemic drug delivery into the inner ear. We report on the first in vitro tests of a new ferrogel consisting of superparamagnetic iron oxide nanoparticles (SPIONs) and a Pluronic (R) F127 (PF127) copolymer. Pluronic copolymers possess a unique viscosity-adjustable property that makes PF127 gels easy to handle compared to conventional cross-linked hydrogels. This ferrogel was successfully tested in cadaver human temporal bones as well as in organotypic explant cultures of mouse inner ears. SPIONs were identified by light microscopy and localized with different imaging modes in energy-filtered transmission electron microscopy. Our approach shows a promising possibility to use iron oxide nanoparticles, which are suitable for visualization and characterization at both the light- and electron-microscopic levels. From the Clinical Editor: The authors report the first in vitro tests of a new ferrogel consisting of superparamagnetic iron oxide nanoparticles (SPIONs) and a Pluronic (R) F127 (PF127) copolymer for drug delivery in the inner ear, demonstrasting a promising possibility to use iron oxide nanoparticles, which are suitable for visualization and characterization at both the light- and electron-microscopic levels.
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