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Ultrasound-assisted nonviral antiangiogenic small interfering RNA delivery for the treatment of cancer.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Ultrasound-assisted nonviral antiangiogenic small interfering RNA delivery for the treatment of cancer./
Author:	Florinas, Stelios.
Description:	1 online resource (168 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 75-12, Section: B.
Contained By:	Dissertations Abstracts International75-12B.
Subject:	Medicine. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3620392click for full text (PQDT)
ISBN:	9781303908347

Ultrasound-assisted nonviral antiangiogenic small interfering RNA delivery for the treatment of cancer.
Florinas, Stelios.

Ultrasound-assisted nonviral antiangiogenic small interfering RNA delivery for the treatment of cancer. - 1 online resource (168 pages)

Source: Dissertations Abstracts International, Volume: 75-12, Section: B.

Thesis (Ph.D.)--The University of Utah, 2014.

Includes bibliographical references

RNA interference (RNAi) therapy is an alternative approach to treat diseases with uncontrolled gene expression such as cancer. Thus, a small interfering RNA (siRNA) with a specific sequence can knockdown the production of one undesirable protein, which is responsible for the evolvement of the disease. The key for successful RNAi therapy is the delivery of genetic material to the right site, at a therapeutic concentration, and at the right time. So far, there has been no clinical impact of RNAi therapeutics due to numerous reasons. To achieve the desired effect of protein knockdown, the siRNA must overcome numerous physiological barriers, enter the cell, and reach the cytosol, where it will be included into the RNAi machinery. Unprotected siRNA is unstable in circulation after systemic injection due to enzymatic degradation, and therefore is unable to accumulate at the target site in a high enough concentration to cause a therapeutic effect. In addition, siRNA shows insufficient cellular uptake efficacy due to electrostatic repulsion between negatively charged siRNA backbone and negatively charged cell membrane. Thus, the design of a gene carrier system that overcomes the aforementioned hurdles in gene delivery is a necessity to achieve a therapeutic effect with the RNAi mechanism. This dissertation focuses on the development and characterization of a gene carrier system that is able to enhance siRNA delivery in vitro as well as in vivo. We combined a bioreducible polymeric polycation (ABP) with microbubbles (MB) and ultrasound (US) to form our newly designed gene carrier system siRNA-ABP-MB (SAM) complexes. SAM complexes can protect siRNA from enzymatic degradation and facilitate cellular uptake. Further, SAM complexes showed improved gene knockdown in cancer cells and improved siRNA uptake in tumor tissue, resulting in decelerating tumor growth in vivo.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9781303908347Subjects--Topical Terms:

641104
Medicine.
Subjects--Index Terms:

CancerIndex Terms--Genre/Form:

542853
Electronic books.

Ultrasound-assisted nonviral antiangiogenic small interfering RNA delivery for the treatment of cancer.
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520 $a RNA interference (RNAi) therapy is an alternative approach to treat diseases with uncontrolled gene expression such as cancer. Thus, a small interfering RNA (siRNA) with a specific sequence can knockdown the production of one undesirable protein, which is responsible for the evolvement of the disease. The key for successful RNAi therapy is the delivery of genetic material to the right site, at a therapeutic concentration, and at the right time. So far, there has been no clinical impact of RNAi therapeutics due to numerous reasons. To achieve the desired effect of protein knockdown, the siRNA must overcome numerous physiological barriers, enter the cell, and reach the cytosol, where it will be included into the RNAi machinery. Unprotected siRNA is unstable in circulation after systemic injection due to enzymatic degradation, and therefore is unable to accumulate at the target site in a high enough concentration to cause a therapeutic effect. In addition, siRNA shows insufficient cellular uptake efficacy due to electrostatic repulsion between negatively charged siRNA backbone and negatively charged cell membrane. Thus, the design of a gene carrier system that overcomes the aforementioned hurdles in gene delivery is a necessity to achieve a therapeutic effect with the RNAi mechanism. This dissertation focuses on the development and characterization of a gene carrier system that is able to enhance siRNA delivery in vitro as well as in vivo. We combined a bioreducible polymeric polycation (ABP) with microbubbles (MB) and ultrasound (US) to form our newly designed gene carrier system siRNA-ABP-MB (SAM) complexes. SAM complexes can protect siRNA from enzymatic degradation and facilitate cellular uptake. Further, SAM complexes showed improved gene knockdown in cancer cells and improved siRNA uptake in tumor tissue, resulting in decelerating tumor growth in vivo.
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