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

Improved Pancreatic Cancer Therapy U...

Tucci, Samantha.

Linked to FindBook

Google Book

Amazon

博客來

Improved Pancreatic Cancer Therapy Using Engineered Gemcitabine Nanoparticles.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Improved Pancreatic Cancer Therapy Using Engineered Gemcitabine Nanoparticles./
Author:	Tucci, Samantha.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	156 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-09, Section: B.
Contained By:	Dissertations Abstracts International80-09B.
Subject:	Biomedical engineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10937835
ISBN:	9780438929845

Improved Pancreatic Cancer Therapy Using Engineered Gemcitabine Nanoparticles.
Tucci, Samantha.

Improved Pancreatic Cancer Therapy Using Engineered Gemcitabine Nanoparticles. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 156 p.

Source: Dissertations Abstracts International, Volume: 80-09, Section: B.

Thesis (Ph.D.)--University of California, Davis, 2018.

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

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer and there is a desperate need for new therapeutic strategies. Very few patients are surgical candidates and chemotherapeutics struggle to breach the characteristically dense and hypovascular microenvironment. Nanotechnology provides a platform that prolongs drug pharmacokinetics and allows for targeted delivery, controlled release, and deposition of higher concentrations of drug at cancerous sites which both enhances the efficacy of treatment and reduces systemic side or adverse effects. Here, multiple strategies to encapsulate gemcitabine, an FDA-approved PDAC chemotherapeutic, into nanoparticles are assessed. First, squalenoylation, or the conjugation of squalene to a desired molecule, is employed to create nanoparticles with high gemcitabine load and improved cellular-level and system-wide drug delivery. Squalenoylation conjugation chemistry was enhanced, increasing yields from 15% to 63%. Additionally, a microfluidic mixing platform was optimized to produce SqGem-based NPs in a reliable and scalable manner. Similar or superior cytotoxicity profiles were achieved for SqGem-based NPs compared to conventional PDAC chemotherapeutics in both human and mouse cell lines of PDAC. SqGem-based NPs were further functionalized with the goal of improving clinical utility: a PDAC targeting peptide was incorporated into SqGem-based NPs and its impact on morphology and cellular trafficking were observed; a 64Cu chelator (2-S-(4-aminobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid) was squalenoylated and used with positron emission tomography imaging to monitor the in vivo fate of SqGem-based NPs; and, albumin was incorporated into SqGem-based NPs, enabling the co-delivery of paclitaxel, another potent chemotherapeutic. Second, gemcitabine was encapsulated in temperature-sensitive liposomes (TSLs). By incorporating copper(II) in the loading buffer and optimizing the lipid composition of the liposomal shell, gemcitabine could be loaded into TSLs (GemTSLs) at up to 12% by weight, 4-fold greater than previously reported values. GemTSLs were efficacious against both murine breast cancer and pancreatic cancer in vitro and they extended the half-life of active gemcitabine in vivo, allowing for lower doses of gemcitabine to achieve the same therapeutic effect. Treatments of GemTSLs plus ultrasound hyperthermia that triggers intravascular release of drug in the target tumor, suppressed tumor growth in the neu deletion line (NDL) model of murine breast cancer and caused greater tumor death when compared to gemcitabine in a more aggressive tumor model of murine pancreatic cancer with low toxicity.

ISBN: 9780438929845Subjects--Topical Terms:

535387
Biomedical engineering.

Improved Pancreatic Cancer Therapy Using Engineered Gemcitabine Nanoparticles.
LDR:03823nmm a2200349 4500 001 2207377
005 20190920101645.5
008 201008s2018 ||||||||||||||||| ||eng d
020 $a 9780438929845
035 $a (MiAaPQ)AAI10937835
035 $a (MiAaPQ)ucdavis:18315
035 $a AAI10937835
040 $a MiAaPQ $c MiAaPQ
100 1 $a Tucci, Samantha. $3 3434364
245 1 0 $a Improved Pancreatic Cancer Therapy Using Engineered Gemcitabine Nanoparticles.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2018
300 $a 156 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-09, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Ferrara, Katherine.
502 $a Thesis (Ph.D.)--University of California, Davis, 2018.
506 $a This item must not be sold to any third party vendors.
520 $a Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer and there is a desperate need for new therapeutic strategies. Very few patients are surgical candidates and chemotherapeutics struggle to breach the characteristically dense and hypovascular microenvironment. Nanotechnology provides a platform that prolongs drug pharmacokinetics and allows for targeted delivery, controlled release, and deposition of higher concentrations of drug at cancerous sites which both enhances the efficacy of treatment and reduces systemic side or adverse effects. Here, multiple strategies to encapsulate gemcitabine, an FDA-approved PDAC chemotherapeutic, into nanoparticles are assessed. First, squalenoylation, or the conjugation of squalene to a desired molecule, is employed to create nanoparticles with high gemcitabine load and improved cellular-level and system-wide drug delivery. Squalenoylation conjugation chemistry was enhanced, increasing yields from 15% to 63%. Additionally, a microfluidic mixing platform was optimized to produce SqGem-based NPs in a reliable and scalable manner. Similar or superior cytotoxicity profiles were achieved for SqGem-based NPs compared to conventional PDAC chemotherapeutics in both human and mouse cell lines of PDAC. SqGem-based NPs were further functionalized with the goal of improving clinical utility: a PDAC targeting peptide was incorporated into SqGem-based NPs and its impact on morphology and cellular trafficking were observed; a 64Cu chelator (2-S-(4-aminobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid) was squalenoylated and used with positron emission tomography imaging to monitor the in vivo fate of SqGem-based NPs; and, albumin was incorporated into SqGem-based NPs, enabling the co-delivery of paclitaxel, another potent chemotherapeutic. Second, gemcitabine was encapsulated in temperature-sensitive liposomes (TSLs). By incorporating copper(II) in the loading buffer and optimizing the lipid composition of the liposomal shell, gemcitabine could be loaded into TSLs (GemTSLs) at up to 12% by weight, 4-fold greater than previously reported values. GemTSLs were efficacious against both murine breast cancer and pancreatic cancer in vitro and they extended the half-life of active gemcitabine in vivo, allowing for lower doses of gemcitabine to achieve the same therapeutic effect. Treatments of GemTSLs plus ultrasound hyperthermia that triggers intravascular release of drug in the target tumor, suppressed tumor growth in the neu deletion line (NDL) model of murine breast cancer and caused greater tumor death when compared to gemcitabine in a more aggressive tumor model of murine pancreatic cancer with low toxicity.
590 $a School code: 0029.
650 4 $a Biomedical engineering. $3 535387
650 4 $a Nanotechnology. $3 526235
650 4 $a Physiology. $3 518431
650 4 $a Oncology. $3 751006
690 $a 0541
690 $a 0652
690 $a 0719
690 $a 0992
710 2 $a University of California, Davis. $b Biomedical Engineering. $3 1035546
773 0 $t Dissertations Abstracts International $g 80-09B.
790 $a 0029
791 $a Ph.D.
792 $a 2018
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10937835