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Responsive Dual Nanoparticle 19F Magnetic Resonance Molecular Imaging Probes.
Responsive Dual Nanoparticle 19F Magnetic Resonance Molecular Imaging Probes.

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자료유형  
 학위논문
Control Number  
0017164976
International Standard Book Number  
9798384441250
Dewey Decimal Classification Number  
616
Main Entry-Personal Name  
Cooke, Daniel J.
Publication, Distribution, etc. (Imprint  
[S.l.] : The University of Texas at Austin., 2024
Publication, Distribution, etc. (Imprint  
Ann Arbor : ProQuest Dissertations & Theses, 2024
Physical Description  
169 p.
General Note  
Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
General Note  
Advisor: Que, Emily L.
Dissertation Note  
Thesis (Ph.D.)--The University of Texas at Austin, 2024.
Summary, Etc.  
요약Noninvasive molecular imaging is a powerful tool for the diagnosis of disease. Magnetic resonance imaging (MRI) is an excellent candidate for molecular imaging due to a lack of ionizing radiation, high spatial resolution and unlimited penetration depth. 19F MRI benefits from a very low biological background signal and can provide complementary information to the more commonly used 1H MRI. This dissertation reports the study of responsive dual nanoparticle molecular imaging probes for 19F MRI. We use perfluorocarbon-encapsulated mesoporous silica nanoparticles (19F-MSNs) bound to a magnetic quencher nanoparticle to modulate the 19F MR signal. The nature of the linkage between the nanoparticles allows for signal "turn-on" in response to an external stimulus, facilitating specific detection of biological analytes or environments.We have developed a dual nanoparticle conjugate probe using superparamagnetic iron oxide nanoparticles (SPIONs) to quench the 19F MR signal of 19F-MSNs. Using DNA aptamers as linkers, a robust 19F MRI response is observed in live mice in the presence of thrombin. The use of DNA aptamers allows for versatility of analyte sensing. Improvements can be made to this probe using two main strategies: 1) Incorporating T1 shortening agents to increase the conspicuity of the probe; 2) Varying the size of the SPION and its distance to 19FMSNs. We propose that paramagnetic MnO nanoparticles incorporated into the perfluorocarbon phase of 19F-MSNs can enhance the 19F T1 relaxation time. The solubilization of MnO in perfluorocarbons necessitates ligand exchange with fluorinated ligands. The size of SPIONs affects their quenching strength and can be easily tuned by changing the synthetic parameters. The distance between SPIONs and 19F-MSNs is tunable by varying the length of the DNA linkers. We discuss methods to enhance the sensitivity of DNC by varying these parameters.Lastly, we are adapting the DNC platform to be a theranostic probe by replacing SPIONs with superparamagnetic FePt nanoparticles. We demonstrate that FePt nanoparticles are cytotoxic due to the release of Fe2+ and Pt2+ at low pH upon cellular uptake. FePt nanoparticles are bound to 19F-MSNs by a pHsensitive linker such that FePt is released from 19F-MSNs in the low pH extracellular tumor microenvironment.
Subject Added Entry-Topical Term  
Medical imaging.
Subject Added Entry-Topical Term  
Molecular biology.
Subject Added Entry-Topical Term  
Nanoscience.
Index Term-Uncontrolled  
Noninvasive molecular imaging
Index Term-Uncontrolled  
Magnetic resonance imaging
Index Term-Uncontrolled  
Nanoparticles
Index Term-Uncontrolled  
Biological analytes
Added Entry-Corporate Name  
The University of Texas at Austin Chemistry
Host Item Entry  
Dissertations Abstracts International. 86-04B.
Electronic Location and Access  
로그인을 한후 보실 수 있는 자료입니다.
Control Number  
joongbu:653646

MARC

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■035    ▼a(MiAaPQ)123vireo24688Cooke
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■0820  ▼a616
■1001  ▼aCooke,  Daniel  J.
■24510▼aResponsive  Dual  Nanoparticle  19F  Magnetic  Resonance  Molecular  Imaging  Probes.
■260    ▼a[S.l.]▼bThe  University  of  Texas  at  Austin.  ▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a169  p.
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-04,  Section:  B.
■500    ▼aAdvisor:  Que,  Emily  L.
■5021  ▼aThesis  (Ph.D.)--The  University  of  Texas  at  Austin,  2024.
■520    ▼aNoninvasive  molecular  imaging  is  a  powerful  tool  for  the  diagnosis  of  disease.  Magnetic  resonance  imaging  (MRI)  is  an  excellent  candidate  for  molecular  imaging  due  to  a  lack  of  ionizing  radiation,  high  spatial  resolution  and  unlimited  penetration  depth.  19F  MRI  benefits  from  a  very  low  biological  background  signal  and  can  provide  complementary  information  to  the  more  commonly  used  1H  MRI.  This  dissertation  reports  the  study  of  responsive  dual  nanoparticle  molecular  imaging  probes  for  19F  MRI.  We  use  perfluorocarbon-encapsulated  mesoporous  silica  nanoparticles  (19F-MSNs)  bound  to  a  magnetic  quencher  nanoparticle  to  modulate  the  19F  MR  signal.  The  nature  of  the  linkage  between  the  nanoparticles  allows  for  signal  "turn-on"  in  response  to  an  external  stimulus,  facilitating  specific  detection  of  biological  analytes  or  environments.We  have  developed  a  dual  nanoparticle  conjugate  probe  using  superparamagnetic  iron  oxide  nanoparticles  (SPIONs)  to  quench  the  19F  MR  signal  of  19F-MSNs.  Using  DNA  aptamers  as  linkers,  a  robust  19F  MRI  response  is  observed  in  live  mice  in  the  presence  of  thrombin.  The  use  of  DNA  aptamers  allows  for  versatility  of  analyte  sensing.  Improvements  can  be  made  to  this  probe  using  two  main  strategies:  1)  Incorporating  T1  shortening  agents  to  increase  the  conspicuity  of  the  probe;  2)  Varying  the  size  of  the  SPION  and  its  distance  to  19FMSNs.  We  propose  that  paramagnetic  MnO  nanoparticles  incorporated  into  the  perfluorocarbon  phase  of  19F-MSNs  can  enhance  the  19F  T1  relaxation  time.  The  solubilization  of  MnO  in  perfluorocarbons  necessitates  ligand  exchange  with  fluorinated  ligands.  The  size  of  SPIONs  affects  their  quenching  strength  and  can  be  easily  tuned  by  changing  the  synthetic  parameters.  The  distance  between SPIONs  and  19F-MSNs  is  tunable  by  varying  the  length  of  the  DNA  linkers.  We  discuss  methods  to  enhance  the  sensitivity  of  DNC  by  varying  these  parameters.Lastly,  we  are  adapting  the  DNC  platform  to  be  a  theranostic  probe  by  replacing  SPIONs  with  superparamagnetic  FePt  nanoparticles.  We  demonstrate  that  FePt  nanoparticles  are  cytotoxic  due  to  the  release  of  Fe2+  and  Pt2+  at  low  pH  upon  cellular  uptake.  FePt  nanoparticles  are  bound  to  19F-MSNs  by  a  pHsensitive  linker  such  that  FePt  is  released  from  19F-MSNs  in  the  low  pH  extracellular  tumor  microenvironment.
■590    ▼aSchool  code:  0227.
■650  4▼aMedical  imaging.
■650  4▼aMolecular  biology.
■650  4▼aNanoscience.
■653    ▼aNoninvasive  molecular  imaging
■653    ▼aMagnetic  resonance  imaging
■653    ▼aNanoparticles
■653    ▼aBiological  analytes
■690    ▼a0565
■690    ▼a0574
■690    ▼a0307
■71020▼aThe  University  of  Texas  at  Austin▼bChemistry.
■7730  ▼tDissertations  Abstracts  International▼g86-04B.
■790    ▼a0227
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164976▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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