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Polymeric micelles as a diagnostic t...

Hoang, Nu Bryan.

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Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer./
作者:	Hoang, Nu Bryan.
面頁冊數:	221 p.
附註:	Source: Dissertation Abstracts International, Volume: 75-11(E), Section: B.
Contained By:	Dissertation Abstracts International75-11B(E).
標題:	Health Sciences, Pharmacy. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3631329
ISBN:	9781321097740

Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer.
Hoang, Nu Bryan.

Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer. - 221 p.

Source: Dissertation Abstracts International, Volume: 75-11(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2014.

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

Block copolymer micelles have emerged as a viable formulation strategy with several drugs relying on this technology in clinical evaluation. To date, information on the tumor penetration and intratumoral distribution of block copolymer micelles (BCM) has been quite limited. Thus, there is impetus to develop a radiolabeled formulation that can be used to gain invaluable insight into the intratumoral distribution of the BCMs. This information could then be used to direct formulation strategies as a means to optimize treatment outcomes.

ISBN: 9781321097740Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer.
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245 1 0 $a Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer.
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500 $a Source: Dissertation Abstracts International, Volume: 75-11(E), Section: B.
500 $a Advisers: Christine J. Allen; Raymond M. Reilly.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2014.
506 $a This item must not be sold to any third party vendors.
520 $a Block copolymer micelles have emerged as a viable formulation strategy with several drugs relying on this technology in clinical evaluation. To date, information on the tumor penetration and intratumoral distribution of block copolymer micelles (BCM) has been quite limited. Thus, there is impetus to develop a radiolabeled formulation that can be used to gain invaluable insight into the intratumoral distribution of the BCMs. This information could then be used to direct formulation strategies as a means to optimize treatment outcomes.
520 $a This thesis describes the synthesis and characterization of a targeted block copolymer micelle system based on poly(ethylene glycol)-block -poly(epsilon-caprolactone) labeled with the radionuclide Indium-111 (111In). The incorporation of the imageable component, 111In permits pursuit of image-guided drug delivery for real-time monitoring of tumor localization and intratumoral distribution. Intracellular trafficking of drugs and therapies such as Auger electron emitting radionuclides to perinuclear and nuclear regions of cells is critical to realizing their full therapeutic potential. HER2 specific antibodies (trastuzumab fab fragments) and nuclear localization signal peptides were conjugated to the surface of the BCMs to direct uptake in HER2 expressing cells and subsequent localization in the cell nucleus. Cell uptake was HER2 density dependent, confirming receptor-mediated internalization of the BCMs. Importantly, conjugation of NLS resulted in a significant increase in nuclear uptake of the radionuclide 111In. Successful nuclear targeting was shown to improve the antiproliferative effect of the Auger electrons. In addition, a significant radiation enhancement effect was observed by concurrent delivery of low-dose MTX and 111In in all breast cancer cell lines evaluated. Imaging enabled the accurate quantification of the specific tumor uptake of the micelles and visualization of their degree of tumor penetration in relation to microvessel density. Ultimately, the 111In-micelles could be used for such diverse applications as detection of malignancies, molecular characterization of tumors, improved therapy guidance and targeted anti-cancer treatment.
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