A Combined Chemical and Magneto-Mechanical Induction of Cancer Cell Death by the Use of Functionalized Magnetic Iron Nanowires

Handle URI:
http://hdl.handle.net/10754/606100
Title:
A Combined Chemical and Magneto-Mechanical Induction of Cancer Cell Death by the Use of Functionalized Magnetic Iron Nanowires
Authors:
Martinez Banderas, Aldo ( 0000-0003-1707-5597 )
Abstract:
Cancer prevails as one of the most devastating diseases being at the top of death causes for adults despite continuous development and innovation in cancer therapy. Nanotechnology may be used to achieve therapeutic dosing, establish sustained-release drug profiles, and increase the half-life of drugs. In this context, magnetic nanowires (NWs) have shown a good biocompatibility and cellular internalization with a low cytotoxic effect. In this thesis, I induced cancer cell death by combining the chemotherapeutic effect of iron NWs functionalized with Doxorubicin (DOX) with mechanical disturbance under a low frequency alternating magnetic field. Two different agents, APTES and BSA, were separately used for coating NWs permitting further functionalization with DOX. Internalization was qualitatively and quantitatively assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal reflection analysis, BSA formulations demonstrate to have a higher internalization degree and a broader distribution within the cells in comparison to APTES formulations. Both groups of functionalized NWs generated a comparable cytotoxic effect in MDA-MB-231 breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by the free DOX (~95% at the same concentration) and non-functionalized NWs formulations (~10% at the same NWs concentration). A synergistic cytotoxic effect is obtained when a low frequency magnetic field (1 mT, 10 Hz) is applied to cells treated with the two formulations that is again comparable (~70% at the highest concentration). Furthermore, the cytotoxic effect of both groups of coated NWs without the drug increased notoriously when the field is applied (~25% at the highest concentration tested). Here, a novel bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of the iron NWs coupled with the chemotoxic effect of an anticancer drug. Moreover, it was demonstrated that iron nanowires possess an outstanding biocompatibility and showed high efficacy as drug delivery agents coupled to a high degree of cell internalization. Finally, the proposed method benefits from the low power fields applied during treatment. This poses much less safety risks and allows using cheaper and simpler equipment.
Advisors:
Kosel, Jürgen ( 0000-0002-8998-8275 )
Committee Member:
Ravasi, Timothy ( 0000-0002-9950-465X ) ; Merzaban, Jasmeen ( 0000-0002-7276-2907 ) ; Fariborzi, Hossein
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience
Program:
Bioscience
Issue Date:
Apr-2016
Type:
Thesis
Appears in Collections:
Theses; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.advisorKosel, Jürgenen
dc.contributor.authorMartinez Banderas, Aldoen
dc.date.accessioned2016-04-20T15:26:45Zen
dc.date.available2016-04-20T15:26:45Zen
dc.date.issued2016-04en
dc.identifier.urihttp://hdl.handle.net/10754/606100en
dc.description.abstractCancer prevails as one of the most devastating diseases being at the top of death causes for adults despite continuous development and innovation in cancer therapy. Nanotechnology may be used to achieve therapeutic dosing, establish sustained-release drug profiles, and increase the half-life of drugs. In this context, magnetic nanowires (NWs) have shown a good biocompatibility and cellular internalization with a low cytotoxic effect. In this thesis, I induced cancer cell death by combining the chemotherapeutic effect of iron NWs functionalized with Doxorubicin (DOX) with mechanical disturbance under a low frequency alternating magnetic field. Two different agents, APTES and BSA, were separately used for coating NWs permitting further functionalization with DOX. Internalization was qualitatively and quantitatively assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal reflection analysis, BSA formulations demonstrate to have a higher internalization degree and a broader distribution within the cells in comparison to APTES formulations. Both groups of functionalized NWs generated a comparable cytotoxic effect in MDA-MB-231 breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by the free DOX (~95% at the same concentration) and non-functionalized NWs formulations (~10% at the same NWs concentration). A synergistic cytotoxic effect is obtained when a low frequency magnetic field (1 mT, 10 Hz) is applied to cells treated with the two formulations that is again comparable (~70% at the highest concentration). Furthermore, the cytotoxic effect of both groups of coated NWs without the drug increased notoriously when the field is applied (~25% at the highest concentration tested). Here, a novel bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of the iron NWs coupled with the chemotoxic effect of an anticancer drug. Moreover, it was demonstrated that iron nanowires possess an outstanding biocompatibility and showed high efficacy as drug delivery agents coupled to a high degree of cell internalization. Finally, the proposed method benefits from the low power fields applied during treatment. This poses much less safety risks and allows using cheaper and simpler equipment.en
dc.language.isoenen
dc.subjectMagnetic Nanowiresen
dc.subjectFunctionalizationen
dc.subjectAlternating magnetic field inductionen
dc.subjectdrug deliveryen
dc.subjectcancer therapyen
dc.subjectnanomedicineen
dc.titleA Combined Chemical and Magneto-Mechanical Induction of Cancer Cell Death by the Use of Functionalized Magnetic Iron Nanowiresen
dc.typeThesisen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentBioscienceen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberRavasi, Timothyen
dc.contributor.committeememberMerzaban, Jasmeenen
dc.contributor.committeememberFariborzi, Hosseinen
thesis.degree.disciplineBioscienceen
thesis.degree.nameMaster of Scienceen
dc.person.id132568en
All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.