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.
|Advisor:||Olsen, Ken W.|
|Commitee:||Crumrine, David, Dale, Rodney, Kanzok, Stefan|
|School:||Loyola University Chicago|
|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|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be