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Polymeric/inorganic multifunctional nanoparticles for simultaneous drug delivery and visualization
KTH, School of Information and Communication Technology (ICT), Material Physics, Functional Materials, FNM.
KTH, School of Information and Communication Technology (ICT), Material Physics, Functional Materials, FNM.
KTH, School of Information and Communication Technology (ICT), Material Physics, Functional Materials, FNM.
KTH, School of Information and Communication Technology (ICT), Material Physics, Functional Materials, FNM.
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2010 (English)In: Materials Research Society Symposium Proceedings, ISSN 0272-9172, E-ISSN 1946-4274, Vol. 1257Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 1257
National Category
Materials Engineering
Identifiers
URN: urn:nbn:se:kth:diva-26782DOI: 10.1557/PROC-1257-O04-03Scopus ID: 2-s2.0-79951616373OAI: oai:DiVA.org:kth-26782DiVA: diva2:372718
Note
QC 20101202Available from: 2010-11-26 Created: 2010-11-26 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Multifunctional nanomaterials for diagnostic and therapeutic applications
Open this publication in new window or tab >>Multifunctional nanomaterials for diagnostic and therapeutic applications
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.
Series
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 2010:11
National Category
Dentistry
Identifiers
urn:nbn:se:kth:diva-26788 (URN)978-91-7415-803-8 (ISBN)
Public defence
2010-12-17, C2, KTH-Electrum, Isafjordsgatan 24, Kista, 13:30 (English)
Opponent
Supervisors
Note
QC 20101207Available from: 2010-12-07 Created: 2010-11-26 Last updated: 2010-12-07Bibliographically approved
2. Chemically Synthesized Nano-Structured Materials for Biomedical and Photonic Applications
Open this publication in new window or tab >>Chemically Synthesized Nano-Structured Materials for Biomedical and Photonic Applications
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nanostructured materials have attracted a broad interest for applications in scientific and engineering fields due to their extraordinary properties stemming from the nanoscale dimensions. This dissertation presents the development of nanomaterials used for different applications, namely biomedicine and dye lasing.

Various inorganic nanoparticles have been developed as contrast agents for non-invasive medical imaging, such as magnetic resonance imaging (MRI) and X-ray computed tomography (CT), owing to their unique properties for efficient contrasting effect. Superparamagnetic iron oxide nanoparticles (SPIONs) are synthesized by thermo-decomposition method and phase-transferred to be hydrophilic used as MRI T2 (negative) contrast agents. Effects of surface modification of SPIONs by mesoporous silica (mSiO2) coating have been examined on the magnetic relaxivities. These contrast agents (Fe3O4@mSiO2) were found to have a coating-thickness dependent relaxation behavior and exhibit much higher contrast efficiency than that for the commercial ones. By growing thermo-sensitive poly(N-isopropylacrylamide -co-acrylamide) (P(NIPAAm-co-AAm)) as the outermost layer on Fe3O4@mSiO2 through free radical polymerization, a multifunctional core-shell nano-composite has been built up. Responding to the temperature change, these particles demonstrate phase transition behavior and were used for thermo-triggered magnetic separation. Their lower critical solution temperature (LCST) can be subtly tuned from ca. 34 to ca. 42 ˚C, suitable for further in vivo applications. An all-in-one contrast agent for MRI, CT and fluorescence imaging has been synthesized by depositing gadolinium oxide carbonate hydrate [Gd2O(CO3)2·H2O] shell on mSiO2-coated gold nanorod (Au NR), and then the particles were grafted with antibiofouling copolymer which can further link with the fluorescent dye. It shows both a higher CT and MRI contrast than the clinical iodine and gadolinium chelate contrast agent, respectively. Apart from the imaging application, owing to the morphology of Au NR, the particle has a plasmonic property of absorbing near-infrared (NIR) irradiation and suitable for future photothermal therapy. Cytotoxicity and biocompatibility of aforementioned nanoparticles have been evaluated and minor negative effects were found, which support their further development for medical applications.

Gold nanoparticles embedded in the optical gain material, water solution of Rhodamine 6G (Rh6G) in particular, used in dye lasers can both increase and damp the dye fluorescence, thus, changing the laser output intensity. The studies of size effect and coating of gold nanoparticles on photostability of the gain media reveal that small sized (ca. 5.5 nm) gold nanoparticles are found detrimental to the photostability, while for the larger ones (ca. 25 nm) fluorescence enhancement rather than quenching is likely to occur. And a noticeable improvement of the photostability for the gain material is achieved when gold is coated with SiO2.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2012. xii, 45 p.
Series
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 2012:12
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-96261 (URN)
Public defence
2012-06-12, Sal/Hall C2, Electrum, KTH-ICT, Isafjordsgatan 26, Kista, 10:00 (English)
Opponent
Supervisors
Note
QC 20120605Available from: 2012-06-05 Created: 2012-05-31 Last updated: 2012-06-05Bibliographically approved

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