Kaitlyn Colglazier

Major: Biomedical Engineering
Purdue School of Engineering and Technology
Supervisor: Joseph Dynlacht, Joy Garrett
Department: Department of Radiation Oncology, Indiana University School of Medicine

Identifying the Effects and Mechanisms of Heat-activated Platinated Phosphines Metalloenediynes in vitro

The objective of my internship was to test drugs that could be used as a cancer treatment as an alternative to chemotherapy or radiation therapy which come with severe side effects. The drugs focused are in this project were platinated phosphines which are metalloenediyne compounds that are known to cause enhancement of DNA damage to cancer cells. When these compounds are exposed to cancer cells and temperatures above the normal human body (hyperthermia), the cancer cells are expected to go through a mechanism of cell death. Clonogenic survival assays were used to determine the toxicity of these drugs on cancer cells when heated. Out of the three variations of platinated phosphines that were tested, PtPP-mMe displayed the highest levels of cell toxicity with heat. An in vitro DNA binding assay was used to test how efficiently the platinated phosphines, specifically Pt-PP, were attaching to the cancer cell’s DNA to contribute to cell death. It showed an insignificant level of binding to DNA which could explain the lack of cytotoxicity in platinated phosphines. Further studies are being done on mice to investigate if platinated phosphines are suitable for cancer treatment at a clinical level.