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Self-Assembled Single Stranded DNA-Amphiphiles for Targeted Drug Delivery
Self-Assembled Single Stranded DNA-Amphiphiles for Targeted Drug Delivery

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자료유형  
 학위논문
Control Number  
0015490336
International Standard Book Number  
9781085762328
Dewey Decimal Classification Number  
616.99
Main Entry-Personal Name  
Harris, Michael.
Publication, Distribution, etc. (Imprint  
[Sl] : University of Minnesota, 2018
Publication, Distribution, etc. (Imprint  
Ann Arbor : ProQuest Dissertations & Theses, 2018
Physical Description  
157 p
General Note  
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
General Note  
Advisor: Kokkoli, Efrosini.
Dissertation Note  
Thesis (Ph.D.)--University of Minnesota, 2018.
Restrictions on Access Note  
This item must not be sold to any third party vendors.
Summary, Etc.  
요약The use of targeted drug delivery has significantly improved the field of medicine in the last 30 years. At the same time, the field of DNA nanotechnology has allowed for the design nanoparticles with exact nanoscale precision. This thesis combines the two fields by using single-stranded DNA amphiphiles, a novel class of biomaterials, to create new targeted drug delivery vehicles.DNA aptamers are a sub-class of single stranded DNA molecules whose three-dimensional structure allows them to bind to one molecule with high affinity. ssDNA-amphiphile micelles were created from a ssDNA aptamer sequence to create a targeted ssDNA micelle for cancer therapies. These targeted micelles were shown to internalize only to cells expressing the aptamer target and release into the cytosol over 24 h. In vivo studies showed that although tumor accumulation of ssDNA-amphiphile micelles is independent of their targeting capability, internalization of the micelles requires the aptamer sequence.DNA-amphiphiles have also been shown to form nanotubes when in aqueous solution, dependent on the exact DNA sequence and lipid tail structure used. One ssDNA-amphiphile that forms nanotubes was used for delivery to mouse glioblastoma cells. The nanotubes were shown to internalize to the glioblastoma cells, but not to healthy mouse astrocytes. When delivered directly to both hemispheres of the brains of mice with tumors in the right hemisphere, retention was observed only in the tumor hemisphere and not in the healthy hemisphere. This observation was conserved when the nanotubes were delivered systemically.The nanotubes were then used for an initial in vitro chemotherapy experiment. When mixed with the chemotherapeutic doxorubicin, the nanotubes released little chemotherapeutic over the course of two weeks, with no significant change in the nanotube structure over this time. When delivered to mouse glioblastoma cells, the doxorubicin - nanotube mixture showed better cell toxicity compared to free doxorubicin. This is a promising result for chemotherapeutic delivery of the nanotubes.
Subject Added Entry-Topical Term  
Chemical engineering
Subject Added Entry-Topical Term  
Nanotechnology
Subject Added Entry-Topical Term  
Oncology
Added Entry-Corporate Name  
University of Minnesota Chemical Engineering
Host Item Entry  
Dissertations Abstracts International. 81-04B.
Host Item Entry  
Dissertation Abstract International
Electronic Location and Access  
로그인을 한후 보실 수 있는 자료입니다.
Control Number  
joongbu:567348

MARC

 008200131s2018                                          c    eng  d
■001000015490336
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■020    ▼a9781085762328
■035    ▼a(MiAaPQ)AAI10838340
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a616.99
■1001  ▼aHarris,  Michael.
■24510▼aSelf-Assembled  Single  Stranded  DNA-Amphiphiles  for  Targeted  Drug  Delivery
■260    ▼a[Sl]▼bUniversity  of  Minnesota▼c2018
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2018
■300    ▼a157  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  81-04,  Section:  B.
■500    ▼aAdvisor:  Kokkoli,  Efrosini.
■5021  ▼aThesis  (Ph.D.)--University  of  Minnesota,  2018.
■506    ▼aThis  item  must  not  be  sold  to  any  third  party  vendors.
■520    ▼aThe  use  of  targeted  drug  delivery  has  significantly  improved  the  field  of  medicine  in  the  last  30  years.  At  the  same  time,  the  field  of  DNA  nanotechnology  has  allowed  for  the  design  nanoparticles  with  exact  nanoscale  precision.  This  thesis  combines  the  two  fields  by  using  single-stranded  DNA  amphiphiles,  a  novel  class  of  biomaterials,  to  create  new  targeted  drug  delivery  vehicles.DNA  aptamers  are  a  sub-class  of  single  stranded  DNA  molecules  whose  three-dimensional  structure  allows  them  to  bind  to  one  molecule  with  high  affinity.  ssDNA-amphiphile  micelles  were  created  from  a  ssDNA  aptamer  sequence  to  create  a  targeted  ssDNA  micelle  for  cancer  therapies.  These  targeted  micelles  were  shown  to  internalize  only  to  cells  expressing  the  aptamer  target  and  release  into  the  cytosol  over  24  h.  In  vivo  studies  showed  that  although  tumor  accumulation  of  ssDNA-amphiphile  micelles  is  independent  of  their  targeting  capability,  internalization  of  the  micelles  requires  the  aptamer  sequence.DNA-amphiphiles  have  also  been  shown  to  form  nanotubes  when  in  aqueous  solution,  dependent  on  the  exact  DNA  sequence  and  lipid  tail  structure  used.  One  ssDNA-amphiphile  that  forms  nanotubes  was  used  for  delivery  to  mouse  glioblastoma  cells.  The  nanotubes  were  shown  to  internalize  to  the  glioblastoma  cells,  but  not  to  healthy  mouse  astrocytes.  When  delivered  directly  to  both  hemispheres  of  the  brains  of  mice  with  tumors  in  the  right  hemisphere,  retention  was  observed  only  in  the  tumor  hemisphere  and  not  in  the  healthy  hemisphere.  This  observation  was  conserved  when  the  nanotubes  were  delivered  systemically.The  nanotubes  were  then  used  for  an  initial  in  vitro  chemotherapy  experiment.  When  mixed  with  the  chemotherapeutic  doxorubicin,  the  nanotubes  released  little  chemotherapeutic  over  the  course  of  two  weeks,  with  no  significant  change  in  the  nanotube  structure  over  this  time.  When  delivered  to  mouse  glioblastoma  cells,  the  doxorubicin  -  nanotube  mixture  showed  better  cell  toxicity  compared  to  free  doxorubicin.  This  is  a  promising  result  for  chemotherapeutic  delivery  of  the  nanotubes.
■590    ▼aSchool  code:  0130.
■650  4▼aChemical  engineering
■650  4▼aNanotechnology
■650  4▼aOncology
■690    ▼a0542
■690    ▼a0652
■690    ▼a0992
■71020▼aUniversity  of  Minnesota▼bChemical  Engineering.
■7730  ▼tDissertations  Abstracts  International▼g81-04B.
■773    ▼tDissertation  Abstract  International
■790    ▼a0130
■791    ▼aPh.D.
■792    ▼a2018
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T15490336▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.
■980    ▼a202002▼f2020

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