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Molecular beacons for cancer treatme...

Stefflova, Klara.

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Molecular beacons for cancer treatment and detection.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Molecular beacons for cancer treatment and detection./
作者:	Stefflova, Klara.
面頁冊數:	204 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7072.
Contained By:	Dissertation Abstracts International67-12B.
標題:	Chemistry, Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3246244

Molecular beacons for cancer treatment and detection.
Stefflova, Klara.

Molecular beacons for cancer treatment and detection. - 204 p.

Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7072.

Thesis (Ph.D.)--University of Pennsylvania, 2006.

The aim of my dissertation work was to synthesize and validate the concept of photodynamic therapy (PDT) beacons that are specific to cancer cell-associated targets that can be simultaneously used for near-infrared (NIR) fluorescence imaging and PDT. I have focused on decreasing the background for imaging and the treatment sideffects. I targeted three groups of molecular fingerprints of cancer cells---unique mRNAs, overexpressed proteases, and cancer-associated receptors---by attaching either DNA, a short peptide, or Folate to the fluorescent photosensitizer Pyropheophorbide a (Pyro). I synthesized three main classes of PDT beacons differing in the quencher attached. The first, so-called "killer beacon", contains carotenoid (Car), quenching both fluorescence and singlet oxygen. The DNA or peptide linker holds the Pyro and Car together until this beacon finds a cancer-specific mRNA or protease. Once the DNA linker hybridizes to a mRNA target or the target protease cleaves the peptide linker, Pyro and Car are no longer in close proximity and both fluorescence and 1O 2 production are restored, thus imaging and consequently killing the diseased cells. This concept was validated in solution by monitoring the 1O2 and fluorescence restoration and partly also in cells. The second class has no quencher to reduce the light-dependent toxicity or fluorescence. It uses a short hydrophilic peptide and Folate (targeting cancer-overexpressed folate receptor) attached to Pyro to enhance cancer selectivity. The cell work and in vivo biodistribution revealed the positive impact of peptide on tumor-selective uptake and avoidance of liver and spleen. Because of their excellent biodistribution, the probes in this class show particular promise for clinical applications. The third class contains a fluorescence quencher BHQ-3, connected to Pyro through various peptide linkers, serving as substrates for target proteases. These fluorescence-quenched beacons incorporate the lessons learned from experiments on the second class and, depending on their design, they were either proven to be useful for assessing the success of PDT (or other anticancer therapy) by monitoring caspase-3 activity, imaging the sites of apoptosis by restored Pyro fluorescence in situ, or they were shown to identify cells with protease-of-interest expression by restored fluorescence, to focus the subsequent therapy.Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Molecular beacons for cancer treatment and detection.
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