Multifunctional nanomaterials for diagnostic and therapeutic applications
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
Place, publisher, year, edition, pages
Stockholm: KTH , 2010. , xii, 70 p.
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 2010:11
IdentifiersURN: urn:nbn:se:kth:diva-26788ISBN: 978-91-7415-803-8OAI: oai:DiVA.org:kth-26788DiVA: diva2:372726
2010-12-17, C2, KTH-Electrum, Isafjordsgatan 24, Kista, 13:30 (English)
Saulnier, Patrick, Professor
Muhammed, Mamoun, Professor
QC 201012072010-12-072010-11-262010-12-07Bibliographically approved
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