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

Carboplatin: Exploring mechanism of ...

Syracuse University.

Linked to FindBook

Google Book

Amazon

博客來

Carboplatin: Exploring mechanism of action and improved drug delivery (1) Role of carbonate in the mechanism of action of carboplatin; (2) Cytotoxicity of mesoporous silica nanomaterials.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Carboplatin: Exploring mechanism of action and improved drug delivery (1) Role of carbonate in the mechanism of action of carboplatin; (2) Cytotoxicity of mesoporous silica nanomaterials./
Author:	Di Pasqua, Anthony J.
Description:	177 p.
Notes:	Adviser: James C. Dabrowiak.
Contained By:	Dissertation Abstracts International69-10B.
Subject:	Chemistry, Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3333564
ISBN:	9780549861201

Carboplatin: Exploring mechanism of action and improved drug delivery (1) Role of carbonate in the mechanism of action of carboplatin; (2) Cytotoxicity of mesoporous silica nanomaterials.
Di Pasqua, Anthony J.

Carboplatin: Exploring mechanism of action and improved drug delivery (1) Role of carbonate in the mechanism of action of carboplatin; (2) Cytotoxicity of mesoporous silica nanomaterials. - 177 p.

Adviser: James C. Dabrowiak.

Thesis (Ph.D.)--Syracuse University, 2008.

(1) The second generation Pt2+ anticancer drug carboplatin, cis-[Pt(NH3)2(CBDCA-O,O')], where CBDCA is cyclobutane-1,1-dicarboxylate, is here shown to react with carbonate, which is present in blood, interstitial fluid, cytosol, and culture medium, to produce platinum-carbonato and -hydroxo complexes, using 1D 13C and 1H NMR spectroscopy, 2D [1H, 15N] HSQC NMR spectroscopy and 15N-labeled carboplatin, an UV-visible spectroscopy. Observed rate constants for the reaction of carboplatin in various media show that CO32- is an important nucleophile for the ring opening of carboplatin, and that this reaction is important in the nucleophile-rich RPMI culture medium. In the presence of Jurkat cells, carboplatin is modified not only by substances present in culture medium, such as carbonate, but also by substances released by the c themselves. Using 13C NMR, resonances have been detected that, by comparison to previously reported carbonato complexes, are due to carbonato species produced when carboplatin is allowed to react in carbonate buffer. This corroborates [1H,15N] HSQC NMR, which shows the formation of carbonato and hydroxo complex cis-[Pt(NH3) 2(CO3)(OH)]-. The products formed in this reaction are taken up by cells a interact with critical cellular components. Aging carboplatin in carbonate buffer produces species that are more toxic toward human neuroblastoma, renal proximal tubule, and Namalwa-luc Burkitt's lymphoma cells, than is intact carboplatin. When exposed to carboplatin or carboplatin aged in carbonate, normal Jurkat cells take up/bind approximately the same amount of Pt, while cisplatin-resistant Jurkat cells take up/bind less Pt when exposed to the latter. Collectively, the studies presented here show that carbonate may play an important role in the mechanism of action of carboplatin in vivo.

ISBN: 9780549861201Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Carboplatin: Exploring mechanism of action and improved drug delivery (1) Role of carbonate in the mechanism of action of carboplatin; (2) Cytotoxicity of mesoporous silica nanomaterials.
LDR:03511nmm 2200289 a 45 001 867333
005 20100804
008 100804s2008 ||||||||||||||||| ||eng d
020 $a 9780549861201
035 $a (UMI)AAI3333564
035 $a AAI3333564
040 $a UMI $c UMI
100 1 $a Di Pasqua, Anthony J. $3 1036058
245 1 0 $a Carboplatin: Exploring mechanism of action and improved drug delivery (1) Role of carbonate in the mechanism of action of carboplatin; (2) Cytotoxicity of mesoporous silica nanomaterials.
300 $a 177 p.
500 $a Adviser: James C. Dabrowiak.
500 $a Source: Dissertation Abstracts International, Volume: 69-10, Section: B, page: .
502 $a Thesis (Ph.D.)--Syracuse University, 2008.
520 $a (1) The second generation Pt2+ anticancer drug carboplatin, cis-[Pt(NH3)2(CBDCA-O,O')], where CBDCA is cyclobutane-1,1-dicarboxylate, is here shown to react with carbonate, which is present in blood, interstitial fluid, cytosol, and culture medium, to produce platinum-carbonato and -hydroxo complexes, using 1D 13C and 1H NMR spectroscopy, 2D [1H, 15N] HSQC NMR spectroscopy and 15N-labeled carboplatin, an UV-visible spectroscopy. Observed rate constants for the reaction of carboplatin in various media show that CO32- is an important nucleophile for the ring opening of carboplatin, and that this reaction is important in the nucleophile-rich RPMI culture medium. In the presence of Jurkat cells, carboplatin is modified not only by substances present in culture medium, such as carbonate, but also by substances released by the c themselves. Using 13C NMR, resonances have been detected that, by comparison to previously reported carbonato complexes, are due to carbonato species produced when carboplatin is allowed to react in carbonate buffer. This corroborates [1H,15N] HSQC NMR, which shows the formation of carbonato and hydroxo complex cis-[Pt(NH3) 2(CO3)(OH)]-. The products formed in this reaction are taken up by cells a interact with critical cellular components. Aging carboplatin in carbonate buffer produces species that are more toxic toward human neuroblastoma, renal proximal tubule, and Namalwa-luc Burkitt's lymphoma cells, than is intact carboplatin. When exposed to carboplatin or carboplatin aged in carbonate, normal Jurkat cells take up/bind approximately the same amount of Pt, while cisplatin-resistant Jurkat cells take up/bind less Pt when exposed to the latter. Collectively, the studies presented here show that carbonate may play an important role in the mechanism of action of carboplatin in vivo.
520 $a (2) Mesoporous silica MCM-41 is here shown to adsorb carboplatin, using UV-visible spectroscopy, and [1H,15N] HSQC NMR spectroscopy and 15N-labeled carboplatin. The toxicity of MCM-41, two of its functionalized analogs, and spherical silica nanoparticles, toward human neuroblastoma cells was also investigated. Cytotoxicity, reported in terms of the number of particles required to inhibit normal cell growth by 50%, appears related to the adsorptive surface area of the particle; however, factors such as size and shape also appear to be important. Collectively, these studies explore the suitability of mesoporous silica nanomaterials as vehicles for drug delivery.
590 $a School code: 0659.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Chemistry, Inorganic. $3 517253
690 $a 0487
690 $a 0488
710 2 $a Syracuse University. $3 1017440
773 0 $t Dissertation Abstracts International $g 69-10B.
790 $a 0659
790 1 0 $a Dabrowiak, James C., $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3333564