東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

On the Permeabilisation and Disrupti...

Karshafian, Raffi.

Linked to FindBook

Google Book

Amazon

博客來

On the Permeabilisation and Disruption of Cell Membranes by Ultrasound and Microbubbles.

Record Type:	Electronic resources : Monograph/item
Title/Author:	On the Permeabilisation and Disruption of Cell Membranes by Ultrasound and Microbubbles./
Author:	Karshafian, Raffi.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2010,
Description:	123 p.
Notes:	Source: Dissertations Abstracts International, Volume: 72-06, Section: B.
Contained By:	Dissertations Abstracts International72-06B.
Subject:	Biophysics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR67704
ISBN:	9780494677049

On the Permeabilisation and Disruption of Cell Membranes by Ultrasound and Microbubbles.
Karshafian, Raffi.

On the Permeabilisation and Disruption of Cell Membranes by Ultrasound and Microbubbles. - Ann Arbor : ProQuest Dissertations & Theses, 2010 - 123 p.

Source: Dissertations Abstracts International, Volume: 72-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2010.

This item must not be sold to any third party vendors.

Therapeutic efficacy of drugs depends on their ability to reach the treatment target. Drugs that exert their effect within cells are constrained by an inability to cross the cell membrane. Methods are being developed to overcome this barrier including biochemical and biophysical strategies. The application of ultrasound with microbubbles increases the permeability of cell membranes allowing molecules, which otherwise would be excluded, to enter the intracellular space of cells; a phenomenon known as sonoporation. This thesis describes studies aimed at improving our understanding of the mechanism underpinning sonoporation and of the exposure parameters affecting sonoporation efficiency. Cancer cells (KHT-C) in suspension were exposed to ultrasound and microbubbles-total of 97 exposure conditions. The effects on cells were assessed through uptake of cell-impermeable molecules (10 kDa to 2 MDa FITC-dextran), cell viability and microscopic observations of the plasma membrane using flow cytometry, colony assay and electron microscopy techniques. Sonoporation was a result of the interaction of ultrasound and microbubbles with the cell membrane. Disruptions (30-100 nm) were generated on the cell membrane allowing cell impermeable molecules to cross the membrane. Molecules up to 2 MDa in size were delivered at high efficiency (∼70% permeabilisation). Sonoporation was short lived; cells re-established their barrier function within one minute, which allowed compounds to remain inside the cell. Following uptake, cells remained viable; ∼50% of sonoporated cells proliferated. Sonoporation efficiency depended on ultrasound and microbubble exposure conditions. Microbubble disruption was a necessary but insufficient indicator of ultrasound-induced permeabilisation. The exposure conditions can be tailored to achieve a desired effect; cell permeability of ∼70% with ∼25% cell death versus permeability of ∼35% with ∼2% cell death. In addition, sonoporation depended on position in the cell cycle. Cells in later stages were more prone to being permeabilised and killed by ultrasound and microbubbles. This study indicated that sonoporation can be controlled through exposure parameters and that molecular size may not be a limiting factor. However, the transient nature may necessitate that the drug be in close vicinity to target cells in sonoporation-mediated therapies. Future work will extend the investigation into in vivo models.

ISBN: 9780494677049Subjects--Topical Terms:

518360
Biophysics.
Subjects--Index Terms:

Cell membranes

On the Permeabilisation and Disruption of Cell Membranes by Ultrasound and Microbubbles.
LDR:03624nmm a2200337 4500 001 2269139
005 20200908082339.5
008 220629s2010 ||||||||||||||||| ||eng d
020 $a 9780494677049
035 $a (MiAaPQ)AAINR67704
035 $a AAINR67704
040 $a MiAaPQ $c MiAaPQ
100 1 $a Karshafian, Raffi. $3 3546444
245 1 0 $a On the Permeabilisation and Disruption of Cell Membranes by Ultrasound and Microbubbles.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2010
300 $a 123 p.
500 $a Source: Dissertations Abstracts International, Volume: 72-06, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2010.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Therapeutic efficacy of drugs depends on their ability to reach the treatment target. Drugs that exert their effect within cells are constrained by an inability to cross the cell membrane. Methods are being developed to overcome this barrier including biochemical and biophysical strategies. The application of ultrasound with microbubbles increases the permeability of cell membranes allowing molecules, which otherwise would be excluded, to enter the intracellular space of cells; a phenomenon known as sonoporation. This thesis describes studies aimed at improving our understanding of the mechanism underpinning sonoporation and of the exposure parameters affecting sonoporation efficiency. Cancer cells (KHT-C) in suspension were exposed to ultrasound and microbubbles-total of 97 exposure conditions. The effects on cells were assessed through uptake of cell-impermeable molecules (10 kDa to 2 MDa FITC-dextran), cell viability and microscopic observations of the plasma membrane using flow cytometry, colony assay and electron microscopy techniques. Sonoporation was a result of the interaction of ultrasound and microbubbles with the cell membrane. Disruptions (30-100 nm) were generated on the cell membrane allowing cell impermeable molecules to cross the membrane. Molecules up to 2 MDa in size were delivered at high efficiency (∼70% permeabilisation). Sonoporation was short lived; cells re-established their barrier function within one minute, which allowed compounds to remain inside the cell. Following uptake, cells remained viable; ∼50% of sonoporated cells proliferated. Sonoporation efficiency depended on ultrasound and microbubble exposure conditions. Microbubble disruption was a necessary but insufficient indicator of ultrasound-induced permeabilisation. The exposure conditions can be tailored to achieve a desired effect; cell permeability of ∼70% with ∼25% cell death versus permeability of ∼35% with ∼2% cell death. In addition, sonoporation depended on position in the cell cycle. Cells in later stages were more prone to being permeabilised and killed by ultrasound and microbubbles. This study indicated that sonoporation can be controlled through exposure parameters and that molecular size may not be a limiting factor. However, the transient nature may necessitate that the drug be in close vicinity to target cells in sonoporation-mediated therapies. Future work will extend the investigation into in vivo models.
590 $a School code: 0779.
650 4 $a Biophysics. $3 518360
653 $a Cell membranes
653 $a Microbubbles
653 $a Permeabilization
690 $a 0760
710 2 $a University of Toronto (Canada). $3 1017674
773 0 $t Dissertations Abstracts International $g 72-06B.
790 $a 0779
791 $a Ph.D.
792 $a 2010
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR67704