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Dissertation/Thesis Abstract

Development of folate directed, protein based photodynamic therapy agents
by Jones, RoJenia N., Ph.D., Loyola University Chicago, 2016, 117; 10172408
Abstract (Summary)

To attack cancer cells in a specific manner, we have developed a folate-targeted, photodynamic therapy (PDT) agent. The folate (FA) and the chlorin e6 (Ce6) photosensitizer were attached to bovine serum albumin (BSA) using carbodiimide chemistry. Since over 50% of cancers overexpress folate receptors, FA-BSA-Ce6 can be taken up by them and is an effective PDT agent. Hela cells exposed to FA-BSA-Ce6 in the dark showed no cytotoxicity. Upon exposure to light, the conjugate was dose (time and concentration) dependent. Concentrations less than or equal to 2 µM were not effective at killing Hela cells but concentrations of at 5 µM and above lead to 95% cell death with a 4 min exposure to 660 nm light. Cancer cells are not alone in expressing many folate receptors. Embryos also need folate to support rapid cell division. This suggested that FA-BSA-Ce6 could also be used to study development in zebrafish. We used reverse transcription-polymerase chain reaction (RT-PCR) on total RNA prepared from 9 embryonic stages. Expression was seen in all stages assayed. An antisense and sense riboprobes were generated to perform whole-mount in situ hybridization. All of the stages tested with the antisense probe demonstrated the presence of FOLR1 mRNA, while sense probe assayed at the same stages were negative. Fluorescent-tagged folate living embryos demonstrated bright florescence indicating successful uptake of conjugates.

Indexing (document details)
Advisor: Olsen, Ken W.
Commitee: Crumrine, David, Dale, Rodney, Kanzok, Stefan
School: Loyola University Chicago
Department: Chemistry
School Location: United States -- Illinois
Source: DAI-B 78/03(E), Dissertation Abstracts International
Subjects: Chemistry, Biochemistry, Oncology
Keywords: Angiogenesis inhibitor therapy, Cancer, Cancer management, Cancer treatment, Photodynamic therapy
Publication Number: 10172408
ISBN: 978-1-369-27174-4
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