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Tailored Magnetic Nanoparticles for Direct and Sensitive Detection of Biomolecules in Biological Samples
KTH, School of Information and Communication Technology (ICT), Material Physics (Closed 20120101), Functional Materials, FNM (Closed 20120101).
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2008 (English)In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 8, no 10, 3423-3428 p.Article in journal (Refereed) Published
Abstract [en]

We developed nanoparticles with tailored magnetic properties for sensitive detection of biomolecules directly in biological samples in a single step. Thermally blocked nanoparticles obtained by thermal hydrolysis are mixed with sample solutions and the variation of the magnetic relaxation due to surface binding is used to detect the presence of biomolecules. The binding events significantly increase the hydrodynamic volume of nanoparticles, thus changing their Brownian relaxation frequency which is measured by a specifically developed AC-susceptometer.

The system was tested for the presence of Brucella antibodies in serum samples from infected cows and the surface of the nanoparticles was functionalized with lipopolysaccarides (LPS) from Brucella abortus. The hydrodynamic volume of functionalized particles increased by 25-35% as a result of the binding of the antibodies, as measured by changes in the susceptibility in an alternating magnetic field. The method has shown high sensitivity, with detection limit of 7 nmol·L-1 in serum without any pre-treatment of the biological samples.

The detection method is very sensitive, cost-efficient and versatile, giving a direct indication if the animal is infected or not, making it suitable for point-of care applications. The functionalization of tailored magnetic nanoparticles can be modified to suit numerous homogenous assays for a wide range of applications.

Place, publisher, year, edition, pages
2008. Vol. 8, no 10, 3423-3428 p.
Keyword [en]
BRUCELLA-ABORTUS, RELAXATION, ANTIBODIES, PARTICLES
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:kth:diva-9231DOI: 10.1021/nl8022498ISI: 000259906800064Scopus ID: 2-s2.0-56149116406OAI: oai:DiVA.org:kth-9231DiVA: diva2:37666
Note

QC 20101001

Available from: 2008-10-10 Created: 2008-10-10 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Magnetic nanostructured materials for advanced bio-applications
Open this publication in new window or tab >>Magnetic nanostructured materials for advanced bio-applications
2008 (English)Licentiate thesis, comprehensive summary (Other scientific)
Abstract [en]

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.

Place, publisher, year, edition, pages
Stockholm: KTH, 2008. vii, 59 p.
Series
Trita-ICT/MAP AVH, ISSN 1653-7610 ; 2008:15
National Category
Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-9569 (URN)978-91-7415-184-8 (ISBN)
Presentation
2008-12-08, N1, KTH-Electrum 3, Isafjordsgatan 28 A/D, Kista, 14:00 (English)
Opponent
Supervisors
Note
QC 20101110Available from: 2008-11-21 Created: 2008-11-14 Last updated: 2010-11-10Bibliographically approved
2. 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

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