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Razvoj anizotropnih magnetnih nanodelcev in njihovi magnetno-mehanski učinki v biomedicini
ID Nemec, Sebastjan (Author), ID Kralj, Slavko (Mentor) More about this mentor... This link opens in a new window, ID Kocbek, Petra (Co-mentor)

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Abstract
Nanotehnologija je interdisciplinarno znanstveno področje, ki vključuje raziskave s področja sinteze in vrednotenja nanomaterialov kot tudi njihovo uporabo. V doktorski nalogi smo si zastavili štiri glavne cilje: i) pripraviti anizotropne magnetne nanodelce, ki omogočajo vgradnjo učinkovin in izkoriščanje magnetno-mehanskega učinka, ii) preučiti uporabo anizotropnih magnetnih nanodelcev kot nanodostavni sistem, iii) pripraviti anizotropne magnetne nanodelce, ki omogočajo selektivno ciljanje vlaken amiloida ? in iv) dokazati vpliv anizotropnih magnetnih nanodelcev na strukturo vlaken amiloida ? v vrtečem magnetnem polju. V okviru zastavljenih raziskav smo pripravili anizotropne magnetne nanoverige železovega oksida z oblogo iz silicijevega dioksida z različno morfologijo. Nanoverige z oblogo iz silicijevega oksida smo pripravili s prilagodljivim in vsestranskim postopkom oblaganja s pomočjo na micelih osnovanih struktur. Z razvitim postopkom oblaganja smo nanoverige obložili z mezoporoznim silicijevim dioksidom z natančno definirano morfologijo. Sintezni postopek je omogočal pripravo obloge z radialno usmerjenimi porami v oblogi iz silicijevega dioksida. Debelino obloge in velikost por smo učinkovito nadzorovali s prilagajanjem pogojev postopka oblaganja. Debelino obloge smo lahko spreminjali v območju med 20 nm in 90 nm ter velikost por v območju od nekaj nm do ~40 nm. Magnetne nanoverige z oblogo iz mezoporoznega silicijevega dioksida smo nato uporabili kot nanodostavni sistem za modelno zdravilno učinkovino ibuprofen. V nanodostavni sistem smo vgradili ibuprofen z uporabo dveh postopkov in tako dosegli vsebnost ibuprofena do 45 % (m/m). Sproščanje ibuprofena iz nanodostavnega sistema osnovanega na magnetnih nanoverigah z oblogo iz mezoporoznega silicijevega dioksida je bilo takojšnje. Na površino obloge iz silicijevega dioksida na magnetnih nanoverigah smo vezali različne fluorescenčne molekule, ki omogočajo selektivno ciljanje struktur amiloida beta. Nato smo s takimi fluorescenčno-označenimi nanoverigami proučevali magnetno-mehanski učinek nanoverig na strukturo vlaken amiloida beta v vrtečem zunanjem magnetnem polju. Magnetne nanoverige so v vrtečem magnetnem polju delno razgradile nitasto strukturo amiloida beta v manj definirane manjše koščke pri čemer se je del vlaken adsorbiral na površino nanoverig. Na podlagi rezultatov raziskav v okviru doktorske naloge smo potrdili nov način fizičnega spreminjanja strukture biološke mehke snovi kot so vlakna amiloida beta na nanometrskem nivoju z uporabo anizotropnih magnetnih nanoverig in vrtečega zunanjega magnetnega polja. Potrditev koncepta magnetno-mehanskega spreminjanja strukture biološke mehke snovi je pomemben znanstveni dosežek, ki odpira novo vejo raziskav na področju mehanskega vplivanja na biološke tarče z anizotropnimi magnetnimi nanodelci.

Language:Slovenian
Keywords:Anizotropni magnetni nanodelci, magnetne nanoverige, silicijev dioksid, mezoporozni silicijev dioksid, nanodelci jedro-obloga, vlakna amiloida beta, magnetno-mehanski učinek, magnetna hipertermija, Alzheimerjeva bolezen.
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:FFA - Faculty of Pharmacy
Year:2023
PID:20.500.12556/RUL-146928 This link opens in a new window
Publication date in RUL:16.06.2023
Views:242
Downloads:0
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Secondary language

Language:English
Title:Development of anisotropic magnetic nanoparticles and their magneto-mechanical effects in biomedicine
Abstract:
Nanotechnology is an interdisciplinary scientific field that involves research ranging from the synthesis and characterization of nanomaterials to their applications. In this doctoral dissertation, we set four main objectives: i) to prepare anisotropic magnetic nanoparticles that enable the incorporation of drug molecules and perform the magneto-mechanical effect, ii) to study the utilization of anisotropic magnetic nanoparticles as a nanocarriers, iii) to prepare anisotropic magnetic nanoparticles that are able to selectively target amyloid  fibrils, and iv) to prove the influence of anisotropic magnetic nanoparticles on the structure of amyloid beta fibrils in a rotating magnetic field. Within our research, we prepared anisotropic magnetic iron oxide nanochains coated with silicon dioxide with different morphologies by using an adjustable and versatile coating procedure assisted by micellar-based structures. Using our developed coating procedure, we prepared mesoporous silica-coated nanochains with well-defined morphology and radially aligned pores. The coating thickness and pore size could be efficiently changed by adjusting the developed coating procedure. Our approach allows coating with thicknesses ranging from 20 nm to 90 nm and the pore size in the range from a few nm to ~40 nm. Magnetic nanochains coated with mesoporous silica were then used to study the incorporation and delivery of ibuprofen molecules. Ibuprofen was loaded into the mesoporous coating using two different procedures and thus achieved an ibuprofen loading degree of up to 45 wg%. The release of ibuprofen from the nanodelivery system based on the nanochains with mesoporous silica coating was immediate. Various fluorescent probes have been specifically developed for the selective targeting of amyloid beta structures which were then attached to the nanochains. Finally, using these fluorescently-labelled nanochains, we investigated the magneto-mechanical effect generated by nanochains on the structure of amyloid beta fibrils in a rotating magnetic field. The results confirmed that the magnetic nanochains affected the fibrillar structure of the amyloid beta fibrils because smaller and less defined fragments were observed after the magneto-mechanical treatment. Moreover, a part of the mechanically broken fibrils were adsorbed on the surface of the nanochains. In summary, we confirmed a new approach of physical disruption of the structure of a soft biological material such as amyloid beta fibrils at the nanometer scale using anisotropic magnetic nanochains in a rotating magnetic field. A proof of the concept of magneto-mechanical disruption of biological soft materials is, in our opinion, a very important scientific achievement that opens a new branch of research activity in the field of magneto-mechanical actuation of biological targets with anisotropic magnetic nanoparticles.

Keywords:Anisotropic magnetic nanoparticles, magnetic nanochains, silica, mesoporous silica, core-shell nanoparticles, amyloid beta fibrils, magneto-mechanical effect, magnetic hyperthermia, Alzheimer’s disease.

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