Biokompatibilni magnetni nanodelci kot kontrastna sredstva za slikanje z magnetno resonanco s prevleko na osnovi liposomov in eritrocitnih membran

Miklavc, Patricija (avtor), Gunčar, Gregor (mentor)

Svetovna zdravstvena organizacija glede na statistiko smrtnosti zaradi raka ocenjuje, da bo do leta 2030, za približno 17 milijonov smrti na leto odgovoren rak[1]. Kljub razširjenosti rakavih obolenj po svetu, še nismo našli učinkovitega zdravljenja omenjene bolezni. Uporaba nanotehnologije v medicini ima velik potencial za signifikantne izboljšave v preventivi, diagnostiki in zdravljenju raka. Magnetni nanodelci spadajo med biomedicinske nanomateriale in jih lahko uporabljamo v diagnostične ter terapevtske namene, pri čemer z njimi manipuliramo z uporabo neinvazivnega zunanjega magnetnega polja[2][3]. Slikanje z magnetno resonanco (MRI) temelji na jedrni magnetni resonanci in se uporablja kot diagnostična aplikacija za slikanje mehkih tkiv, vendar zaradi nizke intrinzične občutljivosti težko ločujemo med zdravim in tumorskim tkivom[4]. Je neinvazivna tehnika, saj za razliko od drugih metod, kot so CAT (computerized axial tomography), PET (positron emission tomography) in SPECT (single-photon-emission computed tomography), ne temelji na radioaktivnem ali ionizirajočem sevanju. S pomočjo kontrastnih sredstev (KS) in njihovih magnetnih relaksacij izboljšamo ločljivost med zdravimi in tumorskimi tkivi. Zaradi njihovih magnetnih lastnosti, biokompatibilnosti, dobre akumulacije na tarčnih mestih[3] in enostavnih modifikacij njihove površine z ligandi[5][6], takšna KS ponujajo nove pristope pri MRI. Superparamagnetni železov oksidni (Fe3O4) nanodelci, premera do 25 nm[7], so ustrezno občutljivi za MRI pri T2 obteženem slikanju, vendar njihova uporaba v kliničnih aplikacijah ni razširjena, zaradi dvoma o njihovi varnosti. Da bi dokazali varnost uporabe Fe3O4 KS, smo najprej izvedli njihovo sintezo in karakterizacijo, nato smo za njihovo enkapsulacijo pripravili klinično odobrene nosilce, t.j. sintetične liposome, ki predstavljajo enega izmed najbolj kompatibilnih nosilcev do sedaj. Na ta način smo pripravili magnetne liposome. Sledila je enkapsulacija Fe3O4 nanodelcev z eritrocitnimi membranami, ki so biokomatibilne in biorazgradljive. Pri tem smo primerjali lastnosti magnetnih eritrocitnih membran z magnetnimi liposomi. Ideja uporabe eritrocitnih membran za enkapsulacijo Fe3O4 nanodelcev izhaja iz uporabe telesu lastnih celic in s tem zagotavljanje maksimalne biokompatibilnosti enkapsulacijskega sredstva. Enkapsulacija (5,0±0,4) nm Fe3O4 nanodelce v liposome ali eritrocitne membrane je pokazala signifikantno izboljšanje r2 relaksivnosti. r2 vrednosti, izmerjene z 9,4 T MRI napravo, za neenkapsulirane, hidrofilne nanodelce je 12±1 mM−1s−1, za magnetne liposome je 188±2 mM−1s−1, za magnetne eritrocitne membrane pa 270±2 mM−1s−1. Analizo relaksivnosti smo primerjali z zajemanjem MRI slik, poleg tega smo izvedli študijo hemolize, ki je pokazala ustrezne hemokompatibilnostne lastnosti magnetnih eritrocitnih membran. S pridobljenimi podatki povzemamo, da so sintetizirani biokompatibilni magnetni nanodelci z eritrocitnimi membranami učinkovitejše KS kot neenkapsulirani nanodelci ali sintetični magnetni-liposomi pri T2 obteženem slikanju.

• Jezik: Slovenski jezik
• Ključne besede: MRI, Fe3O4 nanodelci, kontrastna sredstva, liposomi, eritrocitne membrane
• Vrsta gradiva: Magistrsko delo/naloga
• Tipologija: 2.09 - Magistrsko delo
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Leto izida: 2021
• PID: 20.500.12556/RUL-133214
• COBISS.SI-ID: 89881859
• Datum objave v RUL: 17.11.2021

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Biocompatible magnetic nanoparticles as contrast agents for magnetic resonance imaging with a coating based on liposomes and erythrocyte membranes

Izvleček

Based on cancer mortality statistics, the World Health Organization estimates that by 2030, approximately 17 million deaths annually will be attributable to cancer[1]. Despite how widespread cancer is, effective treatments for it have yet to be discovered. Nanotechnology has considerable potential for application in medicine to significantly improve cancer screening, diagnostics, and treatment. Magnetic nanoparticles belong among biomedical nanomaterials as they can be used for diagnostic and therapeutic purposes as they can be manipulated using a non-invasive external magnetic field[2][3]. Magnetic Resonance Imaging (MRI) is based on nuclear magnetic resonance and it is used as a diagnostic application for imaging of soft tissue. However, due to its low intrinsic contrast, it is difficult to distinguish between healthy tissue and tumors[4]. As opposed to Computerized Axial Tomography (CAT), Positron Emission Tomography (PET), and Single-Photon Emission Computed Tomography (SPECT), MRI is a non-invasive imaging technique as it does not use radioactive or ionizing radiation. Using contrast agents (KS) and their magnetic relaxations, it is possible to increase the contrast between healthy tissue and tumors. Due to their magnetic properties, biocompatibility, good target site accumulation[3], and simple surface modification with ligands[5][6], such KS have opened up new approaches in MRI. Superparamagnetic iron oxide (Fe3O4) nanoparticles with a critical upper size limit of 25 nm[7] are suitably sensitive for MRI with T2-weighted imaging, but their clinical application is not widespread due to safety concerns. In order to prove that Fe3O4 KS are safe to use, we first synthesized and characterized them, and then prepared clinically approved carriers, i.e. synthetic liposomes, which are one of the most compatible carriers, for encapsulation. Using this method, we prepared magneto-liposomes. In addition to liposome encapsulation, we also encapsulated Fe3O4 nanoparticles in erythrocyte membranes, which are biocompatible and biodegradable. We compared the properties of synthesized magneto-erythrocyte membranes with the magneto-liposomes. The idea of using erythrocyte membranes to encapsulate Fe3O4 nanoparticles is to use the body’s own cells, thereby ensuring maximum biocompatibility of the encapsulation agent. Encapsulation of (5,0±0,4) nm Fe3O4 nanoparticles in liposomes or erythrocyte membranes showed a significant improvement of r2 relaxivity. The r2 value measured using a 9,4 T MRI scanner for non-encapsulated hydrophilic nanoparticles is 12±1 mM−1s−1, for magneto-liposomes 188±2 mM−1s−1, and for magnetic erythrocyte membranes 270±2 mM−1s−1. We compared the relaxivity analysis with MRI image capture and conducted a hemolysis study which showed suitable hemocompatibility properties of magnetic erythrocyte membranes. With the data we collected we can conclude that synthesized biocompatible magnetic nanoparticles with erythrocyte membranes or liposomer are suitable KS for T2-weighted imaging.

• Ključne besede: MRI, Fe3O4 nanoparticles, contrast agents, liposomes, erythrocyte membranes